|
()5,6-DHET Lipid Maps
MS Standard |
CAY-10007264 |
|
|
|
Epoxide hydrolases
convert the EETs into vicinal diols, with the concurrent loss of much of
their biological activity. ()5,(6)-DHET is a substrate for sheep seminal
vesicle COX, producing 5,6-dihydroxy prostaglandin E1 and F1α
metabolites in vitro. |
|
(-)-AS 115 |
CAY-13250 |
|
|
|
AS 115 is a potent
and selective inactivator of KIAA1363, displaying an IC50 value of 150
nM when tested as a racemic mixture in the invasive ovarian cancer cell
line SK0V-3. Treatment of SKOV-3 cells with 10 M AS-115 for 4 hours
significantly reduced the formation of MAGE,
alkyl-lysophosphatidylcholine, and alkyl-lysophosphatidic acid. The
activity of the individual enantiomers of AS 115, i.e. (+)-AS 115 and
(-)-AS 15, has not been determined. |
|
(-)-Blebbistatin |
CAY-13013 |
|
|
|
(-)-Blebbistatin is a
selective cell-permeable inhibitor of non-muscle myosin II ATPases. It
rapidly and reversibly inhibits Mg-ATPase activity and in vitro motility
of non-muscle myosin IIA and IIB for several species (IC50 = 0.5-5.0
μM), while poorly inhibiting smooth muscle myosin (IC50 = 80 μM).
Through these effects, blebbistatin blocks apoptosis-related bleb
formation, directed cell migration and cytokinesis in vertebrate cells.
Blebbistatin is inactivated by UV light, which may be particularly
important in fluorescent cell imaging applications. |
|
(-)-CP 47,497 |
CAY-13218 |
|
|
|
CP 47,497 is a
bicyclic cannabinoid analog with potent analgesic activity. It is
comparable or more potent than Δ9-tetrahydrocannabinol in analgesic,
motor depressant, anticonvulsant, and hypothermic effects in mice, rats,
and dogs. The levorotatory enantiomer, (-)-CP 47,497 avidly binds the
CB1 (Ki =1 nM). |
|
(-)-Deguelin |
CAY-10010706 |
|
|
|
Rotenoids, deriving
from the flavonoid family of compounds, act as chemopreventive agents
that inhibit NADH:ubiquinone oxidoreductase activity and suppress
phorbol ester-induced ornithine decarboxylase (ODC) activity. The
rotenoid compound deguelin, originally isolated from the bark of M.
sericea (Leguminosae) to be used as an insecticide and fish poison, has
chemopreventive and chemosensitizing effects in models of skin, mammary,
colon, and lung carcinogenesis. Deguelin inhibits cell growth (IC50 =
<10-8 M), blocks PI3K/Akt activation, suppresses COX-2 expression, and
induces apoptosis in premalignant and squamous human bronchial
epithelial (HBE) cells without affecting normal HBE cells. At 6 mg/kg,
deguelin induces Parkinsons disease-like symptoms in rats after six days
of subcutaneous infusion, and therefore may also serve as a useful model
for Parkinsons disease research. |
|
()-Methyl Jasmonate |
CAY-9000059 |
|
|
|
The jasmonates are a
group of plant stress hormones that naturally occur in plants following
exposure to certain types of stresses, including pathogen and herbivore
attacks. (+/-)-Methyl jasmonate is a mixture of trans (3R,7R and 3S,7S)
isomers. Methyl jasmonate induces the synthesis of proteinase inhibitors
in plant leaves. In cancer cells, it suppresses proliferation and
induces apoptosis. More
specifically, methyl jasmonate inhibits hexokinase that is bound to
mitochondria. As hexokinase is overexpressed in cancer cells and
contributes to cancer cell growth and survival, methyl jasmonates
disruption of mitochondrial hexokinase activity selectively targets, and
kills, cancer cells. Methyl jasmonate derivatives also have potential as
anti-inflammatory agents |
|
(-)-Nutlin-3 |
CAY-18585 |
|
|
|
The protein p53,
often called the guardian of the genome, is a transcription factor that
is activated in response to cellular stress (low oxygen levels, heat
shock, DNA damage, etc.) and acts to prevent further proliferation of
the stressed cell by promoting cell cycle arrest or apoptosis. Its role
as a tumor suppressor is evident by the observation that approximately
50% of human tumors have mutated or non-functional p53. Mdm2, a key
negative regulator of p53, which is over-expressed in many human tumors,
functions by binding to and targeting p53 for proteasomal degradation.
Nutlin-3 is a potent inhibitor of p53-Mdm2 interaction. (-)-Nutlin-3 is
arbitrarily referred to as enantiomer-a because it appears as the first
peak from chiral purification of racemic nutlin-3 and its absolute
stereocenter assignment is not known. It potently inhibits Mdm2-p53
binding with an IC50 value of 0.09 M, induces the expression of
p53-regulated genes, and exhibits potent antiproliferati
ve activity in cells with functional p53, but not in cells with
mutated p53. (-)-Nutlin-3 inhibits the proliferation of exponentially
growing human skin and murine fibroblasts with IC50 values of 2.2 and
1.3 M, respectively, and induces substantial tumor shrinkage in mice
expressing LnCaP, 22Rv1 or MHM cancer cell lines when treated orally
with a 200 mg/kg dose twice daily for two weeks. |
|
(+)-2,5-epi-Goniothalesdiol |
CAY-10008887 |
|
|
|
Goniothalesdiol,
isolated from the bark of the Malaysian tree G. borneensis, is a
tetrahydrofuran compound known to have significant cytotoxic effects
against P388 murine leukemia cells and pesticidal activities.
(+)-2,5-epi-Goniothalesdiol is a goniothalesdiol analog. Little is known
of its biological activity. |
|
(+)-5-trans Cloprostenol |
CAY-10004970 |
|
|
|
Cloprostenol is a
synthetic derivative of prostaglandin F2α that is used in veterinary
medicine as a luteolytic agent for the induction of estrus and in the
treatment of reproductive disorders in cattle, swine, and horses.
(+)-5-trans Cloprostenol is a minor impurity produced in the synthesis
of (+)-cloprostenol. The (+)-5-trans isomer is 20-fold less active than
the 5-cis form in terminating pregnancy in the hamster. |
|
(+)-AS 115 |
CAY-10009650 |
|
|
|
AS 115 is a potent
and selective inactivator of KIAA1363, displaying an IC50 value of 150
nM when tested as a racemic mixture in the invasive ovarian cancer cell
line SK0V-3. Treatment of SKOV-3 cells with 10 M AS-115 for 4 hours
significantly reduced the formation of MAGE,
alkyl-lysophosphatidylcholine, and alkyl-lysophosphatidic acid. The
activity of the individual enantiomers of AS 115, i.e., (+)-AS 115 and
(-)-AS 15, has not been determined. |
|
(+)-Blebbistatin |
CAY-13165 |
|
|
|
(+)-Blebbistatin is
the inactive enantiomer of (-)-Blebbistatin, which is a selective
inhibitor of non-muscle myosin II ATPases. |
|
(+)-CP 47,497 |
CAY-13219 |
|
|
|
CP 47,497 is a
bicyclic CB analog with potent analgesic activity. It is comparable or
more potent than Δ9-tetrahydrocannabinol in analgesic, motor depressant,
anticonvulsant, and hypothermic effects in mice, rats, and dogs. The
dextrorotatory enantiomer, (+)-CP 47,497 avidly binds the CB1 (Ki = 4.15
nM). |
|
(+)-Fluprostenol
methyl amide |
CAY-10010406 |
|
|
|
Fluprostenol is an
F-series prostaglandin analog which has been approved for many years as
a luteolytic in veterinary animals. The isopropyl ester of fluprostenol
(travoprost) is an effective ocular hypotensive drug. (+)-Fluprostenol
is the optically active enantiomer of fluprostenol and would be expected
to have twice the potency as the racemic mixture. (+)-Fluprostenol
methyl amide is a methyl amide analog of (+)-fluprostenol. There are no
published reports on the biological activity of (+)-fluprostenol methyl
amide. |
|
(+)-Fluprostenol methyl ester |
CAY-10010151 |
|
|
|
Fluprostenol is an
F-series prostaglandin analog which has been approved for many years as
a luteolytic in veterinary animals. The isopropyl ester of fluprostenol
(travoprost) is an effective ocular hypotensive drug. CAY10532 is a
methyl ester analog of fluprostenol. Fluprostenol methyl ester promotes
hair growth at concentration of 0.01 and 0.1%. |
|
(+)-Goniothalesdiol |
CAY-10008886 |
|
|
|
(+)-Goniothalesdiol
is a substituted tetrahydrofuran that can be isolated from the bark of
the Malaysian tree, G. borneensis. It has been shown to have promising
cytotoxic activity against p388 murine leukemia cells (ED50 ≥30 g/ml). |
|
(+)-Nutlin-3 |
CAY-10009816 |
|
|
|
The protein p53,
often called the guardian of the genome, is a transcription factor that
is activated in response to cellular stress (low oxygen levels, heat
shock, DNA damage, etc.) and acts to prevent further proliferation of
the stressed cell by promoting cell cycle arrest or apoptosis. Its role
as a tumor suppressor is evident by the observation that approximately
50% of human tumors have mutated or non-functional p53. Mdm2, a key
negative regulator of p53, which is over-expressed in many human tumors,
functions by binding to and targeting p53 for proteasomal degradation.
Nutlin-3 is a potent inhibitor of p53-Mdm2 interaction. (+)-Nutlin-3 is
arbitrarily referred to as enantiomer-b because it appears as the second
peak from chiral purification of racemic nutlin-3 and its absolute
stereocenter assignment is not known. It is 150-fold less potent as an
inhibitor of p53-Mdm2 interaction than (-)-nutlin-3, demonstrating an
IC50 value of 13.6 M. This inactive enantiomer can serve as a useful
control for non Mdm2-related cellular activities. |
|
()-Blebbistatin |
CAY-13186 |
|
|
|
()-Blebbistatin is a
selective cell-permeable inhibitor of non-muscle myosin II ATPases. It
rapidly and reversibly inhibits Mg-ATPase activity and in vitro motility
of non-muscle myosin IIA and IIB for several species (IC50 = 0.5-5.0
μM), while poorly inhibiting smooth muscle myosin (IC50 = 80 μM).
Through these effects, blebbistatin blocks apoptosis-related bleb
formation, directed cell migration and cytokinesis in vertebrate cells.
Blebbistatin is inactivated by UV light, which may be particularly
important in fluorescent cell imaging applications. Purified enantiomers
of Blebbistatin are also available from Cayman ((-)-Blebbistatin 13013;
(+)-Blebbistatin 13165). |
|
()-CP 55,940 |
CAY-13241 |
|
|
|
()-CP 55,940 was one
of the first bicyclic mimetics of Δ9-THC found to have superior
analgesic properties. The racemic
mixture of CP 55,940 is 20- to 100-fold more effective than Δ9-THC in
altering the reactions to thermal, mechanical and chemical pain in mice
(e.g., 50% maximum possible effect (MPE50) observed in the tail clamp
assay at 0.46 and 29.1 mg/kg for ()-CP 55,940 and Δ9-THC,
respectively). CP 55,940 has also been used to identify and characterize
the central cannabinoid receptor, CB1, in rat brain membranes. The
capacity to displace CP 55,940 from CB1 in rat brain preparations has
frequently been used in the characterization of novel cannabimimetics. |
|
1,2-dioleoyl-sn-glycero-3-Phosphatidylcholine |
CAY-10009873 |
|
|
|
1,2-Dioleoyl PC
(DOPC) is a dimonounsaturated fatty acid frequently composed into a
phospholipid bilayer. Because it forms neutral liposomes, DOPC is
commonly used for efficieint in vivo delivery of short interferingRNA
(siRNA). |
|
10-Acetyl-3,7-dihydroxyphenoxazine |
CAY-10010469 |
|
|
|
10-Acetyl-3,7-dihydroxyphenoxazine (ADHP) is a highly sensitive, stable
substrate for horseradish peroxidase (HRP) that is selective towards
H2O2. This colorless, non-fluorescent reagent reacts with H2O2 to
produce the fluorescent compound resorufin, which can be analyzed using
an excitation wavelength of 520-550 nm and an emission wavelength of
585-595 nm. In a 96-well plate format, ADHP enables detection of H2O2 at
a concentration as low as 5 pmol per 100 l sample. |
|
12-oxo Leukotriene B4 |
CAY-20140 |
|
|
|
Leukotriene B4 (LTB4)
is a dihydroxy fatty acid derived from arachidonic acid through the 5-LO
pathway. It promotes a number of leukocyte functions including
aggregation, stimulation of ion fluxes, enhancement of lysosomal enzyme
release, superoxide anion production, chemotaxis, and chemokinesis.
12-oxo LTB4 is an initial metabolite of LTB4 formed via the LTB4
12-hydroxydehydrogenase pathway. It is rapidly converted to
10,11-dihydro-12-oxo-LTB4, followed by reduction of the 12-oxo group to
give 10,11-dihydro-LTB4. 12-oxo-LTB4 (EC50 = 33 nM) is about 70-fold
less potent than LTB4 (EC50 = 0.46 nM) at stimulating Ca2+ mobilization
in human neutrophils. It is also significantly less potent than LTB4 at
stimulating neutrophil migration with EC50 values of 170 and 2.7 nM for
12-oxo-LTB4 and LTB4, respectively. |
|
13(S)-acetoxy-13-HODE
methyl ester |
CAY-10008885 |
|
|
|
13(S)-Hydroxyoctadecadienoic acid (13(S)-HODE) is a 15-lipoxygenase
metabolite of linoleic acid produced in endothelial cells, leukocytes,
and tumor cells. The biological effects of 13(S)-HODE include inhibition
of tumor cell adhesion to the endothelium at concentrations around 1 M,
and down regulation of IRGpIIb/IIIa receptor expression. 13(S)-HODE
methyl ester is a neutral, more lipophilic form of the free acid that
can be used as an analytical standard for 13(S)-HODE. 13(S)-acetoxy-HODE
methyl ester is the acetoxy protected version of 13(S)-HODE methyl
ester. There are no published reports about its biological activity. |
|
13,14-dihydro-15-keto
Prostaglandin A2 Lipid Maps MS Standard |
CAY-10007200 |
|
|
|
PGE2 is metabolized
rapidly to 13,14-dihydro-15-keto PGE2, which is present in the plasma of
humans and other mammals. 13,14-dihydro-15-keto PGA2 results from the
non-enzymatic dehydration of 13,14-dihydro-15-keto PGE2, a process which
is accelerated by the presence of albumin. Further decomposition of
13,14-dihydro-15-keto PGA2 by the intentional addition of base produces
bicyclo PGE2, a stable marker of PGE2 biosynthesis. |
|
13,14-dihydro-15-keto
Prostaglandin D2 Lipid Maps MS Standard |
CAY-10007208 |
|
|
|
13,14-dihydro-15-keto
Prostaglandin D2 (13,14-dihydro-15-keto PGD2) is a metabolite of PGD2
which is formed through the 15-hydroxy PGDH pathway.
13,14-dihydro-15-keto PGD2 was recently identified as a selective
agonist for the CRTH2/DP2 receptor. It also inhibits ion flux in a
canine colonic mucosa preparation. In humans, 13,14-dihydro-15-keto PGD2
is further metabolized to give 11β-hydroxy compounds which have also
undergone β-oxidation of one or both side chains. Virtually no
13,14-dihydro-15-keto PGD2 survives intact in the urine. |
|
13,14-dihydro-15-keto
Prostaglandin E2 Lipid Maps MS Standard |
CAY-10007214 |
|
|
|
13,14-dihydro
Prostaglandin E2 (13,14-dihydro-15-keto PGE2) is the primary metabolite
of PGE2 in plasma. Endogenous or infused PGE2 is rapidly metabolized by
the enzymes 15-hydroxy PGDH and 15-oxo-prostaglandin Δ13-reductase to
form 13,14-dh-15-keto PGE2. 13,14-dh-15-keto PGE2 accumulates to
detectable levels; plasma levels in humans are between 10-100 pg/ml. It
undergoes further metabolism and chemical decomposition, giving it a
relatively short half-life. In dogs, the plasma half-life of
13,14-dh-15-keto PGE2 is about 9 minutes. In humans the metabolite has a
similar short half-life, making it a poor choice of analytes for assays
designed to measure total PGE2 biosynthesis. |
|
13,14-dihydro-15-keto
Prostaglandin F2.alpha. Lipid Maps MS Standard |
CAY-10007226 |
|
|
|
13,14-dihydro-15-keto
Prostaglandin F2α (13,14-dh-15-k PGF2α) is the first prominent plasma
metabolite of PGF2α in the 15-hydroxy PGDH pathway. Measurement of
13,14-dihydro-15-keto PGF2α in plasma can be used as a marker of the in
vivo production of PGF2α. |
|
14,15-EE-(8Z)-E |
CAY-10010486 |
|
|
|
Epoxyeicosatrienoic
acids (EETs), such as 11(12)-EET and 14(15)-EET, are cytochrome P450
metabolites of arachidonic acid that have been identified as
endothelium-derived hyperpolarizing factors with vasodilator activity.
14,15-EE-(8Z)-E is a structural analog of 14(15)-EET that demonstrates
potent vasodilator agonist activity in bovine coronary arteries similar
to that of 14(15)-EET. |
|
14,15-Leukotriene E4 |
CAY-10011362 |
|
|
|
Leukotrienes (LTs)
are a group of acute inflammatory mediators derived from arachidonic
acid in leukocytes. The majority of these metabolites are formed through
the 5-lipoxygenase (5-LO) pathway. 14,15-LTE4 is a metabolite of
14,15-LTC4 and 14,15-LTD4, an alternate class of LTs synthesized by a
pathway involving the dual actions of 15- and 12-LOs on arachidonic acid
via 15-HpETE and 14,15-LTA4 intermediates. These metabolites are
classified as eoxins because they are formed mostly by eosinophils. Mast
cells and nasal polyps can synthesize 14,15-LTC4 as well, however
metabolism to 14,15-LTE4 in these cells and tissue has not been
documented. 14,15-LTE4 increases vascular permeability of human
endothelial cell monolayers with about 10-fold less potency compared
LTC4, but approximately 100-fold greater potency than histamine. |
|
15(S)-HETE Lipid Maps
MS Standard |
CAY-10007251 |
|
|
|
15(S)-HETE is a major
arachidonic acid metabolite from the 15-lipoxygenase pathway. In
mammals, 15(S)-HETE is synthesized in the respiratory epithelium,
leukocytes, and reticulocytes. 15(S)-HETE is present in g/ml
concentrations in the nasal secretions of allergic rhinitis. |
|
15-deoxy-Δ12,14-Prostaglandin J2 Lipid Maps MS Standard |
CAY-10007235 |
|
|
|
15-deoxy-Δ12,14-Prostaglandin J2 (15-deoxy-Δ12,14-PGJ2) is formed from
PGD2 by the elimination of two molecules of water. It binds selectively
to PPARγ with an EC50 value of 2 M in a murine chimera system.
15-deoxy-Δ12,14-PGJ2 is more potent than PGD2, Δ12-PGJ2, and PGJ2 in
stimulating lipogenesis in C3H10T1/2 cells. The EC50 value for induction
of adipocyte differentiation in cultured fibroblasts is 7 M. |
|
15-Lipoxygenase Inhibitor I |
CAY-10010468 |
|
|
|
Lipoxygenases (LOs)
are non-heme iron-containing dioxygenases that catalyze the oxidation of
polyunsaturated fatty acids to generate unsaturated fatty acid
hydroperoxides. The immediate products of 15-LO fatty acid oxidation act
as mediators in inflammation, thrombosis, and cancer. 15-LO inhibitor 1
is a heterocyclic pyrimidobenzothiazine compound that inhibits 15-LO
with an IC50 value of 18 M. The inhibitor appears to act as an
antioxidant, interfering with the redox cycle of 15-LO. |
|
16(R)-HETE |
CAY-10004385 |
|
|
|
Electrolyte and fluid
transport in the kidney are regulated in part by arachidonic acid and
its metabolites. 16-HETE is a minor CYP450 metabolite of arachidonic
acid released by the kidney upon angiotensin II stimulation that
demonstrates stereospecific biological activity. 16(S)-HETE inhibits
proximal tubule ATPase activity by as much as 60% at a concentration of
2 M. |
|
16(R)-Iloprost |
CAY-13076 |
|
|
|
Iloprost is a second
generation structural analog of prostacyclin (PGI2) with about ten-fold
greater potency than the first generation stable analogs, typified by
carbaprostacyclin. Iloprost binds with equal affinity to the recombinant
human IP and EP1 receptors with a Ki of 11 nM. Most preparations of
iloprost contain 16(S) and 16(R) stereoisomers. 16(R)-Iloprost inhibits
platelet aggregation with an IC50 value of 65 nM. |
|
16(S)-HETE |
CAY-10004384 |
|
|
|
Electrolyte and fluid
transport in the kidney are regulated in part by arachidonic acid and
its metabolites. 16-HETE is a minor CYP450 metabolite of arachidonic
acid released by the kidney upon angiotensin II stimulation that
demonstrates stereospecific biological activity. 16(S)-HETE inhibits
proximal tubule ATPase activity by as much as 60% at a concentration of
2 M. |
|
16(S)-Iloprost |
CAY-13077 |
|
|
|
Iloprost is a second
generation structural analog of prostacyclin (PGI2) with about ten-fold
greater potency than the first generation stable analogs, typified by
carbaprostacyclin. Iloprost binds with equal affinity to the recombinant
human IP and EP1 receptors with a Ki of 11 nM. Most preparations of
iloprost contain 16(S) and 16(R) stereoisomers. 16(S)-Iloprost potently
inhibits platelet aggregation with an IC50 value of 3.5 nM. |
|
17(R)-HETE |
CAY-10010637 |
|
|
|
Electrolyte and fluid
transport in the kidney are regulated in part by arachidonic acid and
its metabolites. 17-HETE is a cytochrome P450 (CYP450) metabolite of
arachidonic acid that has stereospecific effects on sodium transport in
the kidney. 17(R)-HETE is an inactive isomer of 17-HETE, whereas the (S)
enantiomer can inhibit proximal tubule ATPase activity at a
concentration of 2 M. |
|
17(R)-Resolvin D1 |
CAY-13060 |
|
|
|
Resolvins are a
family of potent lipid mediators derived from both eicosapentaenoic acid
(EPA) and docosahexaenoic (DHA). In addition to being anti-inflammatory,
resolvins promote the resolution of the inflammatory response back to a
non-inflamed state. Resolvin D1 is produced physiologically from the
sequential oxygenation of DHA by 15- and 5-lipoxygenase. 17(R)-Resolvin
D1 is an aspirin-triggered epimer of resolvin D1 that reduces human
polymorphonuclear leukocyte (PMN) transendothelial migration, the
earliest event in acute inflammation, with equipotency to resolvin D1
(EC50 ~30 nM). 17(R)-Resolvin D1 exhibits a dose-dependent reduction in
leukocyte infiltration in a murine model of peritonitis with maximal
inhibition of ~35% at a 100 ng dose. In contrast to resolvin D1, the
aspirin-triggered form resists rapid inactivation by eicosanoid
oxidoreductases. |
|
17(S)-HETE |
CAY-10011305 |
|
|
|
Electrolyte and fluid
transport in the kidney are regulated in part by arachidonic acid and
its metabolites.17-HETE is a cytochrome P450 (CYP450) metabolite of
arachidonic acid that has stereospecific effects on sodium transport in
the kidney.17(S)-HETE inhibits proximal tubule ATPase activity by as
much as 70% at a concentration of 2 M. |
|
17-keto-(4Z,7Z,10Z,13Z,15E,19Z)-Docosahexaenoic Acid |
CAY-9000346 |
|
|
|
DHA is an essential
fatty acid and the most abundant ω-3 fatty acid in neural tissues,
especially in the retina and brain. 17-keto-(4Z,7Z,10Z,13Z,15E,19Z)-DHA
is a metabolite of lipoxygenase oxidation of DHA and may serve as a
useful standard for studying this biochemical pathway. Keto fatty acids
exhibit a variety of biological activities (e.g., plant growth
regulators, anti-inflammatory lipid mediators), however the activity of
this compound has not been reported. |
|
17-keto-(7Z,10Z,13Z,15E,19Z)-docosapentaenoic acid |
CAY-9000347 |
|
|
|
Docosapentaenoic acid
(DPA) is a ω-3 fatty acid found in fish oils
7-keto-(7Z,10Z,13Z,15E,19Z)-DPA is a metabolite of lipoxygenase
oxidation of DPA and may serve as a useful standard for studying this
biochemical pathway. Keto fatty acids exhibit a variety of biological
activities (e.g., plant growth regulators, anti-inflammatory lipid
mediators,) however the activity of this compound has not been reported |
|
18-carboxy dinor Leukotriene B4 |
CAY-20170 |
|
|
|
18-carboxy dinor
Leukotriene B4 (18-carboxy dinor LTB4) is a β-oxidation metabolite of
LTB4. In the liver, LTB4 is rapidly metabolized to 20-carboxy LTB4,
which then undergoes β-oxidation to 18-carboxy dinor LTB4. |
|
1-Deoxynojirimycin
(hydrochloride) |
CAY-10011718 |
|
|
|
Many glycoproteins
cannot be secreted or expressed without appropriate glycosylation and
subsequent deglucosylation in the endoplasmic reticulum (ER), making
a-glucosidase activity important to proper cell function. a-Glucosidases
I and II remove glucose residues from N-linked oligosaccharides attached
to nascent glycoproteins in the ER enabling transit to the Golgi in
their properly folded form. 1-Deoxynojirimycin (hydrochloride) (dNM
(hydrochloride)), produced by Bacillus species, is a glucose analog that
potently inhibits a-glucosidase I and II. It prevents the formation of
complex N-linked oligosaccharides in yeast and intact mammalian cells by
inhibiting both a-glucosidase I and II with IC50 values of ~2 M. The FDA
has granted orphan drug designation to dNM (hydrochloride) for the
treatment of Pompe disease, an inherited lysosomal storage disorder
caused by a mutation that alters the structure and stability of
a-glucosidase. dNM at a concentration 0.4 mM also inhibits virus spread
in HIV-infected lymphocyte cultures by interfering with a-glucosidase
activity. |
|
1-NBD-decanoyl-2-decanoyl-sn-glycerol |
CAY-9000341 |
|
|
|
Diacylglycerols (DAG)
are produced by the hydrolysis of membrane phospholipids. They act as
lipid second messengers, activating PKC and regulating cell growth and
apoptosis. They also serve as
substrates for DAG kinases for the production of phosphatidic acid,
another important lipid messenger. 1-NBD-decanoyl-2-decanoyl-sn-glycerol
has the fluorophore nitrobenzoxadiazole (NBD) attached to the ?-end of
the terminal decanoyl chain of the model DAG,
1,2-didecanoyl-sn-glycerol.
Fluorescently-tagged lipids have been used to study their interactions
with proteins, their utilization by cells and liposomes, and for the
development of assays for lipid metabolism. |
|
1-Stearoyl-2-Arachidonoyl-sn-Glycerol-d8 |
CAY-10009872 |
|
|
|
SAG-d8 contains eight
deuterium atoms at the 5, 6, 8, 9, 11, 12, 14, and 15 positions. It is
intended for use as an internal standard for the quantification of SAG
by GC- or LC-mass spectrometry. Many protein kinase C (PKC) isoforms
require activation via second messengers including Ca2+, diacylglycerol
(DAG), and/or a phospholipid in order to phosphorylate target proteins,
initiating a variety of important signaling cascades.
1-Stearoyl-2-arachidonoyl-sn-glycerol (SAG) is a DAG that contains the
ω-6 polyunsaturated fatty acid arachidonic acid in the sn-2 position and
stearic acid in the sn-1 position of the glycerol backbone. It can
potently activate PKCα, PKCε, and PKCδ at nM concentrations. Independent
of PKC signaling, SAG competitively binds to the Ras activator RasGRP
with a Ki value of 4.49 M in Jurkat T-cells. |
|
2-(3-Pyridyl)-4-methyl-thiazole-5-Carboxylic Acid |
CAY-13036 |
|
|
|
2-(3-Pyridyl)-4-methyl-thiazole-5-carboxylic acid is a synthetic
intermediate useful for pharmaceutical synthesis. |
|
2,3-dihydrothieno-Thiadiazole carboxylate |
CAY-10011048 |
|
|
|
1,2,3-Thiadiazoles
have diverse applications in medicine and agriculture, such as
bactericides, fungicides, and antiviral agents.
2,3-dihydrothieno-Thiadiazole carboxylate (MTCC), 100 M, both inhibits
and inactivates certain microsomal CYP450 enzymes (CYP2E1 and CYP2B4),
but not others (CYP1A2), with inactivation occurring in a
mechanism-based manner. |
|
2,4-Dichlorophenoxy Acetic Acid |
CAY-10190 |
|
|
|
2,4-Dichlorophenoxy
acetic acid is a synthetic auxin, a class of plant growth regulators,
that is often used as a supplement in plant cell culture media. It is
also an active ingredient in herbicides that controls root elongation
and cell production by disrupting the actin cytoskeleton. |
|
2,4-Dimethylthiazole-5-Carboxylic Acid |
CAY-13233 |
|
|
|
2,4-Dimethylthiazole-5-carboxylic acid is a highly functionalized and
biased thiazole used for drug discovery.
It is used as a heterocyclic building block to specifically
modify lead compounds. |
|
20-hydroxy
Prostaglandin F2α Lipid Maps MS Standard |
CAY-10007229 |
|
|
|
20-hydroxy
Prostaglandin F2α (20-hydroxy PGF2α) is the ω-oxidation product of
PGF2α. Cultured type II alveolar cells from pregnant rabbits metabolize
exogenous PGF2α via microsomal cytochrome P450 ω-oxidation, producing
20-hydroxy PGF2α and its 15-hydroxy PGDH metabolites. Cells from male
rabbits exhibit only the 15-hydroxy PGDH pathway. |
|
2-hydroxy Estradiol |
CAY-13019 |
|
|
|
2-hydroxy Estradiol
(2-HE2) is a cytochrome P450 metabolite of estradiol with low affinity
for estrogen receptors. 2-HE is rapidly metabolized by
catechol-O-methyltransferase (COMT) to form 2-methoxy estradiol (2-ME2)
with a half-life of approximately ten minutes in rat. 2-ME2 has achieved
considerable attention as an anti-cancer agent acting as an angiogenesis
inhibitor via the HIF-1a pathway. Due to the rapid metabolism of 2-HE2,
the effects attributed to 2-HE2, may actually be those of 2-ME2. |
|
2-methoxy Estradiol |
CAY-13021 |
|
|
|
2-methoxy Estradiol
(2-ME2) is a natural metabolite formed by CYP450-mediated hydroxylation
followed by catechol-O-methyltransferase (COMT) methylation of
estradiol. Administration of 2-hydroxy estradiol (2-HE2) to rats results
in formation and clearance of 2-ME2 with t1/2 values of 7.9 and 24.9
minutes, respectively. 2-ME2 exhibits no affinity for estrogen
receptors. 2-ME2 has achieved considerable attention as an anti-cancer
agent acting as an angiogenesis inhibitor via the HIF-1a pathway. The
levels of COMT and 2-ME2 are significantly lower in women with severe
pre-eclampsia. |
|
2-methylbenzamide Oxime |
CAY-13002 |
|
|
|
2-methylbenzamide
Oxime is a synthetic intermediate useful for pharmaceutical synthesis. |
|
2-pyridylamid Oxime |
CAY-13003 |
|
|
|
2-pyridylamid Oxime
is a synthetic intermediate useful for pharmaceutical synthesis. |
|
3-hexanoyl-NBD
Cholesterol |
CAY-13221 |
|
|
|
3-hexanoyl-NBD-Cholesterol is a fluorescently-tagged cholesterol with
the hydrophilic NBD fluorophore attached to carbon 3, at the hydrophilic
end of cholesterol, separated by a 6-carbon spacer. This design allows
the cholesterol to properly orient in membrane bilayers while the
fluorescent tag is presented outside of the bilayer. This should model
the behavior of cholesterol in membranes better than the previously-used
25-NBD cholesterol, which positions NBD directly on the 25th carbon of
cholesterol at the hydrophobic terminus. Fluorescently-tagged lipids
have been used to study their interactions with proteins, their
utilization by cells and liposomes, and for the development of assays
for lipid metabolism. |
|
3-hydroxy-3-methylglutaryl-Coenzyme A-d3 (ammonium salt) |
CAY-9000368 |
|
|
|
3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) is the precursor of
mevalonic acid in the cholesterol biosynthetic pathway. |
|
3-methylbenzamide Oxime |
CAY-13057 |
|
|
|
2-methylbenzamide
Oxime is a synthetic intermediate useful for pharmaceutical synthesis. |
|
3-PT-PtdIns
(3,4,5)-P3 (1,2-dioctanoyl) (sodium salt) |
CAY-10009804 |
|
|
|
The
phosphatidylinositols (PtdIns) phosphates represent a small percentage
of total membrane phospholipids. However, they play a critical role in
the generation and transmission of cellular signals. PtdIns(4,5)-P2 can
be phosphorylated by phosphoinositide (PI)-3-kinase to make
PtdIns(3,4,5)-P3 which initiates an intricate signaling cascade that has
been implicated in cancer. 3-PT-PtdIns(3,4,5)-P3 is an analog of
PtdIns-(3,4,5)-P3 that is resistant to hydrolysis by PTEN. It has a
5-fold reduced affinity for the specific PtdIns(3,4,5)-P3-binding
protein Grp1 and increases sodium transport in A6 cell monolayers. |
|
3-pyridylamid Oxime |
CAY-13004 |
|
|
|
3-pyridylamid Oxime
is a synthetic intermediate useful for pharmaceutical synthesis. |
|
4,5-diphenyl-1,2,3-Thiadiazole |
CAY-10011040 |
|
|
|
1,2,3-Thiadiazoles
have diverse applications in medicine and agriculture, including as
bactericides, fungicides, and antiviral agents.
4,5-diphenyl-1,2,3-Thiadiazole is, at 100 μM, an inhibitor of some
CYP450 enzymes (CYP2B4, CYP1A2), but not others (CYP2E1), with
inhibition occurring in a mechanism-based manner. |
|
4-hydroxy Nonenal
Mercapturic Acid-d3 |
CAY-9000348 |
|
|
|
4-hydroxy Nonenal
mercapturic acid-d3 contains three deuterium atoms at the terminal
methyl position. It is intended for use as an internal standard for the
quantification of 4-hydroxy nonenal mercapturic acid by GC- or LC-mass
spectrometry. Peroxidation of common ω-6 polyunsaturated fatty acids
(PUFAs) such as linoleic acid, DGLA, and arachidonic acid can give rise
to 4-HNE. 4-HNE is cleared rapidly from the plasma and undergoes
enterohepatic circulation as a glutathione conjugate in the rat. About
two thirds of an administered dose of 4-HNE is excreted within 48 hours
in the urine, primarily in the form of mercapturic acid conjugates. The
C-1 aldehyde of 4-HNE is reduced to an alcohol in about half of these
metabolites. The remainder are C-1 aldehydes or have been oxidized to
C-1 carboxylic acids. These aldehydes and carboxylic acids can also form
γ-lactols and γ-lactones, respectively, producing at least four or five
end urinary metabolites of 4-HNE in vivo. |
|
4-phenyl-5-methyl-1,2,3-Thiadiazole |
CAY-10011049 |
|
|
|
Cytochrome P450
(CYP450) enzymes are a superfamily of oxidative catalysts important in
the biosynthesis and metabolism of a wide range of endogenous molecules
as well as the metabolism of xenobiotics. For example, CYP2B4
metabolizes substituted amines, CYP2E1 metabolizes various alcohols and
halogenated alkenes, and CYP1A2 catalyzes the oxygenation of aromatic
compounds and polycyclic hydrocarbons.
4-phenyl-5-methyl-1,2,3-Thiadiazole is a selective, mechanism-based
inhibitor of CYP2B4 and CYP2E1 at a concentration of 100 M that does not
inactivate CYP1A2. 1,2,3-Thiadiazole compounds and their derivatives,
including 4-phenyl-5-methyl-1,2,3-thiadiazole, are also commonly used as
fungicides, herbicides, and plant growth regulators. |
|
4-pyridylamid Oxime |
CAY-13005 |
|
|
|
4-pyridylamid Oxime
is a synthetic intermediate useful for pharmaceutical synthesis. |
|
4-Pyridylthioamide |
CAY-13056 |
|
|
|
4-Pyridylthioamide is
a synthetic intermediate useful for pharmaceutical synthesis. |
|
5-(galactosylhydroxy)-L-Lysine |
CAY-10010255 |
|
|
|
Glycosylated
hydroxylysine residues present in bone type I collagen are terminal
degradation products of the bone matrix that are released during bone
resorption and excreted in the urine. 5-(galactosylhydroxy)-L-Lysine
levels are elevated in patients with metabolic bone loss and thus may
serve as a biochemical marker of bone collagen quality. |
|
5(S),14(R)-Lipoxin B4 |
CAY-90420 |
|
|
|
Lipoxins are a series
of anti-inflammatory lipid mediators whose brief appearance generally
signals the resolution of inflammation. Lipoxin A4 (LXA4) is a potent
inhibitor of leukotriene-triggered polymorphonuclear neutrophil
(PMN)-endothelial cell interaction and also blocks PMN migration
stimulated by leukotriene B4 (LTB4). LXB4 is a positional isomer of LXA4
produced by the metabolism of 15-HETE or 15-HpETE by human leukocytes.
At a concentration of 10-7 M, LXB4 inhibits PMN migration stimulated by
LTB4 and inhibits LTB4-induced adhesion of PMNs with an IC50 value of ~3
X 10-10 M. |
|
5(S),6(R),15(R)-Lipoxin A4 |
CAY-90415 |
|
|
|
Lipid-derived
lipoxins are produced at the site of vascular and mucosal inflammation
where they down-regulate polymorphonuclear leukocyte recruitment and
function. 5(S),6(R),15(R)-Lipoxin A4 (5(S),6(R),15(R)-LXA4) is derived
from the aspirin-triggered formation of 15(R)-HETE from arachidonic
acid. 5(S),6(R),15(R)-LXA4 inhibits LTB4-induced chemotaxis, adherence,
and transmigration of neutrophils
with twice the potency of LXA4 demonstrating activity in the nM range.
The anti-inflammatory effects of aspirin may be ascribed in part to the
ability of 5(S),6(R),15(R)-LXA4 to regulate leukocyte function. |
|
5(S),6(R)-Lipoxin
A4-d5 |
CAY-10007737 |
|
|
|
5(S),6(R)-Lipoxin
A4-d5 (5(S),6(R)-LXA4-d5) contains five deuterium atoms at the 19, 19,
20, 20, and 20 positions. It is intended for use as an internal standard
for the quantification of 5(S),6(R)-LXA4 by GC- or LC-mass spectrometry
(MS). 5(S),6(R)-Lipoxin A4 is a trihydroxy fatty acid containing a
conjugated tetraene, produced by the metabolism of 15-HETE or 15-HpETE
with human leukocytes. 5(S),6(R)-Lipoxin A4 is equipotent to leukotriene
B4 (LTB4) in inducing superoxide generation in human neutrophils at 0.1
M. 5(S),6(R)-Lipoxin A4 is associated with several other biological
functions including leukocyte activation, chemotaxis effects, natural
killer cell inhibition, and monocyte migration and adhesion. |
|
5-methyl-2-deoxy
Cytidine EIA Kit |
CAY-589324 |
|
|
|
DNA methylation is an
important epigenetic process regulating gene expression. Methylation
occurs on carbon 5 of 2-deoxy cytidine yielding the modified base
5-methyl-2-deoxy cytidine. The methylation pattern of cells is tightly
regulated during development with the methylation profile being
transmitted from parent to daughter cells during cell division.
Methylation results in long-term silencing of genes, while unmethylated
regions of DNA can be actively transcribed. |
|
|
|
One region of the
genome of particular interest in regard to methylation is CpG islands.
CpG islands are regions approximately 200 bp to several thousand bp in
length which often span the promoter and first few exons of many
housekeeping and tumor suppressor genes. These regions remain
essentially unmethylated throughout development. As the name implies,
the CpG dinucleotide is overrepresented in CpG islands, with the
frequency being approximately five times greater in CpG islands than in
the remainder of the genome. It is well established that alterations in
DNA methylation are a common feature of cancer. |
|
|
|
In addition to global
genomic hypomethylation, there are also discrete areas of dense
hypermethylation particularly in the normally unmethylated CpG islands.
Because many tumor suppressor genes contain CpG islands, these genes are
among those silenced by hypermethylation. The first report of
methylation of a tumor suppressor CpG island was Retinoblastoma (Rb)
which was discovered in 1989. Interestingly, the pattern and level of
gene hypermethylation for a given cancer is specific to that malignancy,
with cancer of the GI tract tending to show a greater level of
hypermethylation than do other cancers. In the digestive tract,
methylation of genes, including the estrogen receptor, occurs as a
normal part of the aging process. During carcinogenesis, this
age-related methylation may progress to hypermethylation. |
|
|
|
Global changes in
methylation can be quantified by measuring plasma or urinary levels of
5-methyl-2-deoxy cytidine. These changes in methylation can provide
valuable information about cancer status of an individual. For example,
patients with leukemia excrete significantly elevated levels of
5-methyl-2-deoxy cytidine compared to healthy individuals. Global
methylation within tissues can be measured in a similar manner, allowing
study of tissue-specific changes that occur as a result of
differentiation, aging, or carcinogenesis. DNA methylation is regulated
by a family of DNA methyltransferases |
|
|
|
(DNMTs), with DNMT1,
DNMT3a, and DNMT3b all implicated in carcinogenesis. |
|
|
|
Three cytosine
nucleoside analogs (azacitidine, decitabine, and zebularine) which
incorporate into DNA during synthesis are being actively investigated as
anti-cancer drugs. DNMTs bind irreversibly to these cytidine analogs,
resulting in suppression of methylation and the possibility that genes
which had been inappropriately methylated may resume their normal
function. Caymans 5-methyl-2-deoxy Cytidine EIA is a competitive assay
that can be used for the quantification of 5-methyl-2-deoxy cytidine in
urine, culture supernatants, plasma, and other sample matrices. The EIA
typically displays IC50 (50% B/B0) and IC80 (80% B/B0) values of
approximately 12 and 3 ng/ml, respectively. |
|
5-trans Latanoprost
(free acid) |
CAY-10129 |
|
|
|
Latanoprost is an
F-series prostaglandin (PG) analog which has been approved for use as an
ocular hypotensive drug. Latanoprost is an isopropyl ester, a prodrug
form which is converted to latanoprost (free acid) by endogenous
esterase enzymes. The free acid form is 200 times more potent than
latanoprost as a ligand for the human recombinant FP receptor. 5-trans
Latanoprost (free acid) is an isomer of latanoprost (free acid) wherein
the double bond between carbons 5 and 6 has been changed from cis (Z) to
trans (E). The trans isomer of latanoprost occurs as an impurity in
commercial preparations of the bulk drug product. The present compound
was prepared primarily as an analytical standard for detection and
quantitation of this impurity. From what can be inferred from the study
of other trans isomers of F-type prostaglandins, the biological activity
of this isomer is likely to be similar to that of the cis isomer.
However, there are no specific published reports on the biological
activity, and on reducing intraocular pressure in particular, of 5-trans
latanoprost |
|
6-Aminonicotinamide |
CAY-10009315 |
|
|
|
6-Aminonicotinamide
(6-AN) is a well-established inhibitor of the NADP+-dependent enzyme,
6-phosphogluconate dehydrogenase (Ki = 0.46 μM). Through this action,
6-AN interferes with glycolysis, resulting in ATP depletion and
synergizes with DNA-crosslinking chemotherapy drugs, like cisplatin, in
killing cancer cells (IC50 = 0.5 mM). 6-AN also reduces cardiovascular
oxidative injury following ischemia/reperfusion. In addition, 6-AN
causes glial neurodegeneration. |
|
6-keto Prostaglandin E1 Lipid Maps MS Standard |
CAY-10007210 |
|
|
|
6-keto Prostaglandin E1 (6-keto PGE1) is a stable non-enzymatic
hydrolysis product of prostacyclin (PGI2). 6-keto PGE1 is a metabolite
isolated after the incubation of PGI2 with rabbit liver microsomes.
However, it is not produced in appreciable amounts following IV infusion
of PGI2 in humans. 6-keto PGE1 is equipotent with PGI2 as a vasodilator;
in most other aspects its activity resembles PGE1. |
|
7-AAD Cell Viability Kit |
CAY-10009856 |
|
|
|
Evaluation of cell
viability is essential in cell biology and drug discovery. Caymans 7-AAD
Cell Viability Assay Kit employs 7-AAD as a fluorescent label for dead
cells. 7-AAD is a fluorescent dye which is excluded from live cells but
penetrates dead or damaged cells to label DNA. Although 7-AAD
fluorescence is less intense than that of propidium iodide, it exhibits
a higher wavelength emission maximum (excitation at 488 nm, emission at
650 nm) and thus has minimal spectral overlap with PE or FITC. This
makes 7-AAD preferable as a viability marker when FITC and/or PE are
used simultaneously to label surface or intracellular antigens. A
fixative/actinomycin D solution is included in the kit for cell fixation
and blocking, making subsequential immunostaining of
surface/intracellular antigens possible. This kit provides a convenient
tool to quantify cytotoxic effects of environmental toxins or drug
candidates. |
|
7-Aminoclonazepam-d4 |
CAY-10010670 |
|
|
|
Clonazepam is an
anticonvulsant used for several types of seizures, including myotonic or
atonic seizures, photosensitive epilepsy, and absence seizures, although
tolerance may develop. It is seldom effective in generalized
tonic-clonic or partial seizures. The mechanism of action appears to
involve the enhancement of γ-aminobutyric acid receptor responses. |
|
8,9-EE-(14Z)-E |
CAY-18112 |
|
|
|
14,15-EE-(8Z)-E
(catalog no. 10010486) is a potent vasodilator in bovine coronary
arteries. The synthesis of this analog involves the formation of the
epoxide at the 14,15 double bond, however, epoxidation can also occur at
the 8,9 double bond . 8.9-EE-(14Z)-E is a minor product from the
synthesis of 14,15-EE-(8Z)-E. This compound has not been reported in the
literature, and its biological activity is not known. It may serve as a
tool to verify that the parent compound, 14,15-EE-(8Z)-E, is pure and
does not contain the 8,9 epoxy regioisomer. |
|
8-DY547-cGMP |
CAY-10010109 |
|
|
|
Through activation by
the binding of cyclic nucleotides, cyclic nucleotide-gated (CNG) ion
channels mediate sensory signal transduction in photoreceptors and
olfactory cells. 8-DY547-cGMP is a fluorescently-labeled cyclic
nucleotide that can be used to study CNGA2 channel activation.
8-DY547-cGMP and cGMP open the channel with equal efficiency and control
of the channel activity is rapid and reversible. The fluorescence (DF)
can be determined by using DY647. |
|
8-iso Prostaglandin E2-d4 |
CAY-10011321 |
|
|
|
8-iso Prostaglandin
E2-d4 (8-iso PGE2-d4) contains four deuterium atoms at the hydroxyethyl
3, 3',4, and 4' positions. It is intended for use as an internal
standard for the quantification of 8-iso PGE2 by GC-or LC-mass
spectrometry. 8-iso PGE2 is one of several isoprostanes produced from
arachidonic acid during lipid peroxidation. It is a potent renal
vasoconstrictor in the rat. 8-iso PGE2 inhibits U-46619 or I-BOP-induced
platelet aggregation with IC50 values of 0.5 and 5 M, respectively. When
infused into the renal artery of the rat at a concentration of 4
mg/kg/min, 8-iso PGE2 decreases the GFR and renal plasma flow by 80%
without affecting blood pressure. |
|
8-methyl Nonanoic Acid |
CAY-9000310 |
|
|
|
Capsaicin, the
chemical that imparts the spicy-hot quality of chili peppers, is
produced by the fruits of plants belonging to the Capsicum family.
8-methyl Nonanoic acid is an immediate precursor of capsaicin as well as
a byproduct of capsaicin degradation. Addition of 5 mM isocapric acid
significantly increases the yield of capsaicin in both immobilized and
freely suspended cells of C. frutescens. Capsaicin has reported
antimicrobial properties, however 8-methyl nonanoic acid can act as a
growth substrate in certain bacterial strains. |
|
9β-tetranor-13,14-dihydro-15-keto Prostaglandin F1β |
CAY-16853 |
|
|
|
9β,11α-dihydroxy-15-oxo-2,3,4,5-tetranor prostanoic acid is a major
urinary metabolite of PGE2 that is excreted in guinea pig urine at a
concentration range of 1.34-2.74 g/kg. |
|
A-803467 |
CAY-10012588 |
|
|
|
Nav1.8 is a
tetrodotoxin-resistant (TTX-R) sodium channel with high activation
threshold and slow inactivating kinetics that is highly expressed in
small-diameter sensory neurons and has been implicated in signaling
various types of pain. A-803467 is a sodium channel blocker with
high-affinity and selectivity for inhibiting human Nav1.8 sodium
channels (IC50 = 8 nM when stimulated at half-maximal inactivation and
IC50 = 79 nM at a resting state). This compound is unusual in that it
blocks hNav1.8 at negative resting membrane potentials (many small
molecule sodium channel blockers show a reduced affinity for the resting
state) and does not demonstrate significant frequency-dependent block
during a 10 Hz pulse train. A-803467 dose-dependently reduces behavioral
responses in a variety of neuropathic and inflammatory pain models. |
|
Acenocoumarol |
CAY-10010569 |
|
|
|
Acenocoumarol is an
analog of the oral anticoagulant warfarin that functions by inhibiting
vitamin K epoxide reductase, an enzyme that has a critical role in
enabling blood coagulation. It is a brief-acting compound with a
half-life of about eight hours in plasma, which is four times shorter
than that of warfarin. |
|
Aconitase Assay Kit |
CAY-705502 |
|
|
|
Aconitase is an
iron-sulfur protein containing a [Fe4S4]2+ cluster that catalyzes the
stereospecific isomerization of citrate to isocitrate via cis-aconitate.
Whereas exposure of aconitase to oxidants renders the enzyme inactive,
loss of aconitase activity in cells or in biological samples treated
with pro-oxidants has been interpreted as a measure of oxidative damage.
Cayman's Aconitase Assay Kit provides a simple, reproducible, and
sensitive tool for assaying aconitase from tissue homogenates or cell
lysates. In this assay, citrate is isomerized by aconitase into
isocitrate, which is then converted to a-ketoglutarate in a reaction
catalyzed by isocitric dehydrogenase. These reactions are monitored by
measuring the increase in absorbance at 340 nm associated with the
formation of NADPH. The rate of NADPH production is proportional to
aconitase activity. |
|
Adenosine Receptor
A2A Monoclonal Antibody |
CAY-10011454 |
|
|
|
Adenosine receptor
A2A Monoclonal Antibody (A2AR) is a multi-pass membrane protein that is
normally localized to the plasma membrane. This receptor is part of the
G protein-coupled receptor family that binds adenosine and serves
multiple functions. Antagonists of this receptor have been targeted for
the treatment of Parkinsons disease. Early reports found this receptor
is found primarily in the brain striatum, but is also found in immune
cells and other tissues as well. A2AR is comprised of 412 amino acids
with an expected molecular weight of 45 kDa. However multiple
glycosylation sites exist that may explain the retarded migration
observed by western blotting (45-50 kDa). This antibody has been
extensively characterized and the epitope has been mapped to the third
intracellular loop of the receptor. |
|
AG-370 |
CAY-10010568 |
|
|
|
Protein tyrosine
kinase (PTK) inhibitors are potential antiproliferative agents for
diseases caused by the hyperactivity of PTKs. Tyrphostins are a class of
antiproliferative compounds which selectively inhibit PTKs of key growth
factors such as epidermal growth factor (EGF) or platelet-derived growth
factor (PDGF) by blocking the phosphorylation of specific tyrosine
residues. AG-370 is a selective inhibitor of PDGF receptor kinase with
an IC50 value of 20 M in human bone marrow fibroblasts. It displays
comparatively weak inhibition of the EGF receptor (IC50 = 820 M). |
|
AH 23848 (calcium salt, hydrate) |
CAY-19023 |
|
|
|
Thromboxane (TXA2)
activates the T prostanoid (TP) receptor. Prostaglandin E2 (PGE2)
activates four E prostanoid (EP) receptors, EP1-4. AH-23848 is a dual
antagonist of TP and EP4 receptors. It originally was found to inhibit
TXA2-induced platelet aggregation (IC50 = 0.26 μM) and the contraction
of human bronchial smooth muscle induced by the TP agonist U-46619.
AH-23848 was subsequently demonstrated to impair PGE2-mediated
relaxation of piglet saphenous vein by antagonizing the PGE2 receptor
EP4. By inhibiting EP4, it likewise suppresses serum-induced cAMP
generation, cyclin A synthesis, and the proliferation of fibroblasts, as
well as reduces metastasis in a murine model of metastatic breast
cancer. |
|
AL-34662 |
CAY-10011546 |
|
|
|
The transduction of
neurobehavioral effects by serotonin (5-hydroxy tryptamine; 5-HT) is
mediated via at least six major 5-HT receptor subtypes, including 5-HT2.
AL 34662 is a potent 5-HT2 receptor agonist with ocular hypotensive
activity. It binds to the human and rat 5-HT2 receptors in cerebral
cortex homogenates with IC50 values of 1.5 and 0.77 nM, respectively. AL
34662 binds to the recombinant human 5-HT2A, 5-HT2B, and 5-HT2C
receptors with IC50 values of 14.5, 8.1, and 3 nM, respectively. In
ocular hypertensive cynomolgus monkey eyes, AL 34662 lowered intraocular
pressure (IOP) 25% at a dose of 100 g and 33% at 300 g (six hours post
dose) with minimal side effects. |
|
Albumin (bovine) Acetylated |
CAY-10010566 |
|
|
|
Acetylated BSA may be
used as a positive control for ELISA or WB when employing an
acetyl-lysine monoclonal or polyclonal antibody. Caymans Acetyl Lysine
Monoclonal Antibody (clone 7F8) (Catalog No. 10010567) can detect less
than 1 ng of this positive control by immunoblotting. Dilutions from a 1
mg/ml stock solution and 2X Laemmli Buffer may be prepared for WB use.
For example, dissolve the 1 mg lyophilized protein in 1 ml of purified
water (aliquot and freeze for later, use as needed), then make ten-fold
dilutions until the desired concentration range is obtained. Finally
dilute the product 1:1 in 2X Laemmli Buffer. Incubate the prepared
sample for five minutes in boiling water followed by five minutes on ice
prior to loading gels. Histone subunit modifications such as lysine
acetylation are regulated by the
activity of histone acetyltransferases (HATs) and histone deacetylases
(HDACs). Epigenetic modifications such as protein acetylation directly
influence cellular genetic programs including those contributing to
cancer cell viability. |
|
Aldehyde Reactive Probe |
CAY-10009350 |
|
|
|
DNA is continually
damaged by endogenous and environmental agents leading to the formation
of abasic (apurinic/apyrimidinic, AP) sites that are disruptive to DNA
synthesis. Aldehyde Reactive Probe (ARP) is a biotinylated reagent for
the detection and quantification of AP sites in damaged DNA. ARP reacts
with aldehyde groups formed when reactive oxygen species depurinate DNA,
resulting in covalent linkage of biotin to these AP sites. The
biotin-tagged DNA can then be detected using common avidin-conjugated
reporters such as avidin-HRP. The ARP method is highly sensitive,
enabling detection of 2.4 AP sites per 1x107 nucleotides of DNA. |
|
AM630 |
CAY-10006974 |
|
|
|
Cannabinoids produce
biochemical and pharmacological effects by interacting with the central
cannabinoid (CB1) and peripheral cannabinoid (CB2) G protein-coupled
receptors. AM630 is a selective CB2 receptor antagonist that binds to
CB1 and CB2 receptors with Ki values of 5.2 M and 31.2 nM, respectively.
AM630 behaves as an inverse agonist at CB2 receptors, attenuating the
antinociceptive effects of a number of cannabinoids, and as a weak
partial agonist at CB1 receptors. |
|
AMP-Deoxynojirimycin |
CAY-10010332 |
|
|
|
The lipid messenger
ceramide is converted to glucosylceramide by glucosylceramide synthase
(GCS). In the reverse direction, non-lysosomal glucosylceramidase
(GCase), also known as β-glucosidase 2 (BGD), cleaves the glucosyl
moiety from glucosylceramide, liberating ceramide, which can be
converted into sphingomyelin. AMP-deoxynojirimycin (AMP-dNM) is a
hydrophobic derivative of dNM. It potently inhibits BGD (IC50 = 0.3 nM),
less potently antagonizes GCS (IC50 = 25 nM), but only poorly inhibits
other GCase isoforms. AMP-dNM has been shown to strongly suppress
inflammation in a murine model of hapten-induced colitis, enhance
insulin sensitivity in murine and rat models of insulin resistance, and
induce sterol regulatory element-binding protein-regulated gene
expression and cholesterol synthesis in HepG2 cells. |
|
ApoAI (human) EIA Kit |
CAY-500155 |
|
|
|
Apolipoprotein AI
(ApoAI) is a major protein component of HDL. Clinical studies have
demonstrated that lower levels of ApoAI are associated with an increased
risk of myocardial infarction and coronary artery disease.
Overexpression of ApoAI raises HDL cholesterol levels and inhibits the
progression of atherosclerosis in mice. For this reason, upregulation of
ApoAI expression is considered to be one of the most promising
approaches to the development of new therapies for atherosclerosis
targeting HDL. Cayman's ApoAI (human) EIA Kit is an immunometric assay
which can be used to accurately detect and quantify ApoAI in plasma and
serum without prior sample purification. The standard curve spans the
range of 0-20 ng/ml with a limit of detection of approximately 0.3
ng/ml. |
|
ApoAI Monoclonal
Antibody (Clone CC3821C4) |
CAY-13042 |
|
|
|
ApoAI is a major
protein component in high-density lipoproteins (HDL). It acts as an
acceptor for sequential transfers of phospholipids and free cholesterol
from peripheral tissues and transports cholesterol to the liver and
other tissues for excretion and steroidogenesis. Serum ApoAI levels are
inversely related to the risk of developing atherosclerosis.
Loss-of-function mutations are causes of diseases such as HDL deficiency
type 1 (or Tangier disease) and type 2 (familial
hypoalphalipoproteinemia), and systemic non-neuropathic amyloidosis.
Liver and small intestine are two main sources of the protein. ApoAI is
comprised of a single polypeptide chain of 243 amino acid residues with
an estimated molecular weight of 28 kDa. Caymans ApoAI Monoclonal
Antibody detects the protein from diluted human plasma (≤10 g total
protein) by western blotting. Western blotting of recombinant ApoAI
samples suggest a detection limit of 5 ng. |
|
ApoB (human) EIA Kit |
CAY-10011012 |
|
|
|
Apolipoprotein B
(ApoB) is the main apolipoprotein of chylomicrons and low density
lipoproteins (LDL). The protein exists as two main isoforms, ApoB-48 and
ApoB-100. In humans, ApoB-48 and ApoB-100 are synthesized exclusively by
the small intestine and liver, respectively. Elevated plasma
concentrations of ApoB and LDL are established risk factors for
atherosclerotic coronary disease. Caymans Human ApoB EIA Kit is an
immunometric (i.e., sandwich) assay which can be used to measure ApoB in
plasma and serum without prior sample purification. This assay also can
be used to detect cellular ApoB levels in cell lysate samples. The
standard curve spans the range of 0-160 ng/ml with a limit of detection
of approximately 10 ng/ml. |
|
ATB-337 |
CAY-10277 |
|
|
|
Hydrogen sulfide
(H2S) is a naturally occurring gasotransmitter with vasodilator and
inflammatory modulating activity. Non-steroidal anti-inflammatory drugs
(NSAIDs), such as indomethacin, diclofenac, and ibuprofen, are some of
the most commonly used anti-inflammatory drugs available but exhibit
significant side effects, particularly gastric damage, when used
chronically. ATB-337 is a hybrid molecule of an H2S donor and the NSAID
diclofenac. In rats, diclofenac at 10-50 mol/kg caused significant
gastrointestinal damage, whereas no damage was observed with ATB-337
treatment at the same dose. ATB-337 at 50 mol/kg does not promote
leukocyte adherence to vascular endothelium, an effect observed with
diclofenac treatment alone. COX-1 and COX-2 were inhibited with similar
efficacy by diclofenac and ABT-337. An increase in expression of the
pro-inflammatory mediator TNF-α, as well as, the adhesion molecules
ICAM-1 and LFA-1 were not observed in rats treated with 50 mol/kg ABT
-337, effects seen with equimolar doses of diclofenac. These
results indicate that H2S-releasing derivatives of NSAIDs may prove to
be more effective anti-inflammatory agents than traditional NSAIDs
alone. |
|
ATB-343 |
CAY-13045 |
|
|
|
Hydrogen sulfide
(H2S) is a naturally-occurring gasotransmitter with vasodilator and
inflammatory modulating activity. Non-steroidal anti-inflammatory drugs
(NSAIDs), such as indomethacin, diclofenac, and ibuprofen, are some of
the most commonly used anti-inflammatory drugs available but exhibit
significant side effects, particularly gastric damage, when used
chronically. ATB-343 is a hybrid molecule of an H2S donor and the NSAID
indomethacin. In rats, ATB-343 does not cause gastric damage or promote
leukocyte adherence to vascular endothelium, effects which are observed
with indomethacin treatment alone. These results indicate that
H2S-releasing derivatives of NSAIDs may prove to be more effective
anti-inflammatory agents than traditional NSAIDs alone. |
|
Avenanthramide-C
methyl ester |
CAY-10011336 |
|
|
|
Avenanthramide-C
methyl ester is an inhibitor of NF-κB activation that acts by blocking
the phosphorylation of IKK and IκB (IC50 ~ 40 μM). Through this
mechanism, avenanthramide-C methyl ester dose dependently inhibits the
expression and secretion of IL-6, IL-8, and MCP-1 in human aortic
endothelial cells. |
|
BACE (human recombinant) |
CAY-10227 |
|
|
|
Accumulation of the
β-amyloid peptide (Ab) in the brain is implicated as the primary cause
of neurodegeneration and progression of Alzheimers disease (AD). The
β-amyloid peptide is derived from sequential proteolytic cleavage of the
amyloid precursor protein (APP) by β- and γ-secretases. Initial cleavage
by β-secretase (BACE), a membrane-anchored aspartic protease, generates
a soluble N-terminal fragment and a membrane-associated C-terminal
fragment. The C-terminal fragment then undergoes proteolysis by
γ-secretase to give the Ab peptide. BACE has been shown to be the major
β-secretase and a promising target as it initiates the first step in Ab
production. Inhibition of BACE activity could potentially block the
entire cascade of AD pathogenesis. In addition, BACE deficient mice do
not generate Ab peptide. In transgenic murine models of AD driven by Ab
overproduction, BACE deficiency rescued memory deficits and cholinergic
dysfunction. Additionally, the fact that β-secretase is an aspartic
protease has also raised the hope that its therapeutic inhibitor can be
as successful as that against HIV protease. |
|
BACE Inhibitor
Screening Assay Kit |
CAY-600070 |
|
|
|
Accumulation of the
β-amyloid peptide (Ab) in the brain is implicated as the primary cause
of neurodegeneration and progression of Alzheimers disease (AD). The
β-amyloid peptide is derived from sequential proteolytic cleavage of the
amyloid precursor protein (APP) by β- and γ-secretases. Initial cleavage
by β-secretase (BACE; β-site of APP cleaving enzyme), a membrane
anchored aspartic protease, generates a soluble N-terminal fragment and
a membrane-associated C-terminal fragment. The C-terminal fragment then
undergoes proteolysis by γ-secretase to give the Ab peptide. BACE has
been shown to be the major β-secretase and a promising therapeutic
target as this protease initiates the first step in Ab production.
Inhibition of BACE activity could potentially block the entire cascade
of Alzheimers disease pathogenesis. In addition, BACE deficient mice do
not generate Ab peptide. In transgenic murine models of AD driven by Ab
overproduction, BACE deficiency rescued memory deficits and cholinergic
dysfunction. Additionally, the fact that β-secretase is an aspartic
protease has also raised the hope that its therapeutic inhibitor can be
as successful as that against HIV protease. Caymans BACE Inhibitor
Screening Assay Kit provides a convenient method for screening human
BACE inhibitors. The assay utilizes a synthetic Swedish mutant APP
peptide (EVNLDAEF) that has been linked to a fluorophore (EDANS) at one
end and to a nonfluorescent chromophore (Dabcyl) at the other. After
cleavage by BACE, the product (peptide-EDANS) is brightly fluorescent
and can be easily analyzed using a fluorescence plate reader or a
fluorometer with excitation wavelengths of 335-345 nm and emission
wavelengths of 485-510 nm. |
|
BAY-11-7082 |
CAY-10010266 |
|
|
|
The transcription
factor NF-kB plays a key role in regulating over 150 target genes
including the expression of inflammatory cytokines, chemokines,
immunoreceptors, and cell adhesion molecules. In the cytoplasm, inactive
NF-kB complexes are bound to an inhibitor I?B. However in response to
certain stimuli, I?B is phosphorylated, ubiquitinated, and degraded,
enabling the translocation of NF-?B to the nucleus. BAY-11-7082
selectively and irreversibly inhibits NF-?B activation by blocking
TNF-a-induced phosphorylation of I?B-a without affecting constitutive
I?B-a phosphorylation. This compound inhibits the TNF-a-induced surface
expression of adhesion molecules ICAM-1, VCAM-1, and E-selectin in human
endothelial cells with IC50 values of 5-10 M. |
|
BAY-60-7550 |
CAY-10011135 |
|
|
|
The second messengers
cAMP and cGMP are important mediators of signal transduction and hence a
wide range of cellular processes including vasodilation and synaptic
plasticity. Type 2 cyclic nucleotide phosphodiesterases (PDE2) isoforms
inactivate cAMP and cGMP by hydrolyzing the phosphodiester bond.
BAY-60-7550 is a potent PDE2 inhibitor with IC50 values of 2.0 nM
(bovine) and 4.7 nM (human). It is 50-fold more selective for PDE2
compared to PDE1 and greater than 100-fold selective compared to PDE5
PDE3B, PDE4B, PDE7B, PDE8A, PDE9A, PDE10A, and PDE11A. At 3 mg/kg
BAY-60-7550 antagonizes oxidative stress-induced anxiety-like behavioral
effects in mice by decreasing cGMP signaling. At 1 mg/kg BAY-60-7550
improves the performance of rats
in an object location task, enhancing cAMP/cGMP-mediated object and
spatial memory consolidation. |
|
BIO |
CAY-13123 |
|
|
|
BIO is a
cell-permeable bis-indolo (indirubin) compound that acts as a highly
potent, selective, reversible, and ATP-competitive inhibitor of GSK-3α/β
(IC50 = 5 nM). Its specificity has been tested against various
cyclin-dependent kinases (Cdks) (IC50s = 83, 300, 320, and 10,000 nM for
Cdk5/p25, Cdk2/A, Cdk1/B, and Cdk4/D1, respectively). Also specificity
tested were many other commonly studied kinases (IC50 ≥ 10 M),
including MAP kinases, PKA, PKC isoforms, PKG, CK, and IRTK. Inhibition
of GSK by BIO has been shown to result in the activation of the Wnt
signaling pathway and sustained pluripotency in human and murine
embryonic stem cells (ESCs). BIO is reported to maintain self-renewal in
human and murine ESCs as well as induce the differentiation of neonatal
cardiomyocytes. |
|
Bupropion-d9
hydrochloride |
CAY-10010679 |
|
|
|
Bupropion is a
unicyclic, aminoketone antidepressant. The mechanism of its therapeutic
actions is not well understood, but it does appear to block dopamine
uptake. The hydrochloride is available as an aid to smoking cessation
treatment. |
|
C-12 NBD Cholesterol |
CAY-13220 |
|
|
|
3-C-12 NBD
Cholesterol is a fluorescently-tagged cholesterol with the hydrophilic
NBD fluorophore attached to the hydrophilic end of cholesterol,
separated by a 12-carbon spacer. |
|
|
|
This design allows
the cholesterol to properly orient in membrane bilayers while the
fluorescent tag is presented outside of the bilayer.
This should model the behavior of cholesterol in membranes better
than the previously-used C-25 NBD cholesterol, which positions NBD
directly on the 25th carbon of cholesterol at the hydrophobic terminus.
Fluorescently-tagged lipids have been used to study their
interactions with proteins, their utilization by cells and liposomes,
and for the development of assays for lipid metabolism. |
|
C-6 NBD-dihydro-Ceramide |
CAY-10007957 |
|
|
|
C-6 NBD ceramide is a
biologically active fluorescent analog of short chain,
membrane-permeable ceramides. It is as effective as C-6 ceramide in the
inhibition of viral glycoprotein transport through the Golgi. C-6 NBD
ceramide has been used as a fluorescent substrate for the activity of
UDP-glucose:ceramide glucosyltransferase and to demonstrate the
translocation of glucocerebroside and sphingomyelin from the Golgi to
the plasma membrane. C-6 NBD-dihydro-Ceramide is structurally identical
to C-6 NBD ceramide, except it contains a saturated bond in the C-4/C-5
position of the sphingosine backbone. |
|
Cardiogenol C (hydrochloride) |
CAY-13187 |
|
|
|
Most tissues have an
endogenous pool of progenitor cells to draw from upon injury. The adult
heart, however, contains a limited number of undifferentiated cells and
techniques to replicate these cells from other pluripotent tissues have
thus far been nonselective and inefficient. Cardiogenol C is a
diaminopyrimidine compound that induces the differentiation of MHC-
(myosin heavy chain) positive cardiomyocytes from embryonic stem cells
with an EC50 value of 0.1 M. About 90% of embryonic stem cells treated
with 0.25 M cardiogenol C express the cardiac muscle cell specific
transcription factors GATA-4, MEF2, and Nkx2.5 and display the
characteristic beating behavior of differentiated cardiomyocytes. |
|
CAY10506 |
CAY-10009079 |
|
|
|
Anti-diabetic drugs
of the thiazolidinedione (TZD) structural class as well as α-lipoic acid
activate peroxisome proliferator-activated receptor γ (PPARγ), a nuclear
transcription factor that controls glucose metabolism and lipid
homeostasis. CAY10506 is a hybrid lipoic acid-TZD derivative that
transactivates human PPARγ with an EC50 value of 10 M. |
|
CAY10559 |
CAY-10011020 |
|
|
|
Sirtuins (SIRTs)
represent a distinct class of trichostatin A-insensitive
lysyl-deacetylases (class III HDACs). Human SIRT1 is the homolog of
yeast silent information regulator 2 (Sir2) and has been shown to
regulate the activity of the p53 tumor suppressor and inhibit apoptosis.
Small molecule activators of SIRT1, such as resveratrol, extend lifespan
in yeast and C. elegans in a manner that resembles caloric restriction.
CAY10559 is a selective small molecule activator of SIRT1 that is
1,000-fold more potent than resveratrol (EC1.5 = 0.16 M versus EC1.5 =
46.2 M, respectively). In diet-induced obese and diabetic
leptin-defieient ob/ob mice, oral administration of 100 mg/kg CAY10559
once daily improves insulin sensitivity, lowers plasma glucose and
increases mitochondrial capacity after one week of treatment. In Zucker
fa/fa rats, CAY10559 improves whole-body glucose homeostasis and insulin
sensitivity in adipose tissue, skeletal muscle, and liver. |
|
CAY10566 |
CAY-10012562 |
|
|
|
Stearoyl-CoA
desaturase (SCD) catalyzes the committed step of the conversion of
saturated, long-chain fatty acids to monounsaturated fatty acids. The
SCD1 gene is thought to play a key role in lipid homeostasis and body
weight regulation. Thus, modulating SCD1 activity pharmacologically may
be a useful tool for regulating type 2 diabetes, dyslipidemia, and
obesity. CAY10566 is a potent and selective inhibitor of SCD1 that
demonstrates IC50 values of 4.5 and 26 nM in murine and human enzymatic
assays, respectively. This compound inhibits the conversion of
saturated, long-chain fatty acyl-CoAs to monounsaturated, long-chain
fatty acyl-CoAs in HepG2 cells with IC50 values of 7.9 and 6.8 nM,
respectively, when heptadecanoic acid and palmitic acid are used as the
substrate. |
|
CAY10571 |
CAY-10010400 |
|
|
|
Pyridinylimidazoles,
often termed CSAIDs, are a class of anti-inflammatory compounds that
inhibit eicosanoid production and suppress the synthesis of cytokines in
human monocytes. Because of its high specificity, one predominant
pyridinylimidazole, SB203580, is frequently used to inhibit p38 MAPK,
the tyrosine kinase activated by environmental stresses and inflammatory
cytokines. CAY10571 is an analog of SB203580. It inhibits IL-1
production in the human monocytic cell line THP.1 with an IC50 value of
0.20 M and binds CSAID binding protein, a serine/threonine kinase
homologous to p38, inhibiting its kinase activity with an IC50 value of
0.03 M. CAY105571 also inhibits 5-lipoxygenase production in RBL-1 cells
with an IC50 value of 24 M. |
|
CAY10572 |
CAY-18218 |
|
|
|
Cdc7 kinase is a key
regulator of the S-phase of the cell cycle. It is known to promote the
activity of DNA replication origins in eukaryotic organisms. Inhibition
of Cdc7 kinase causes blockade of DNA synthesis in human cell lines.
Tumor cells are then funneled into the apoptotic pathway in a
p53-independent manner. Pharmacological inhibition of Cdc7 kinase can be
an effective strategy for the development of oncologic therapeutics
useful for treatment of cancers. CAY10572 is a potent inhibitor of Cdc7
kinase with an IC50 value of 10 nM in the presence of 1.5 M ATP. At 10
M, CAY10572 induces apoptotic cell death in multiple cancer cell types.
CAY10572 also inhibits Cdk9, a kinase involved in the phosphorylation of
RNA polymerase II and in transcriptional regulation of gene expression,
with an IC50 value of 34 nM. |
|
CAY10573 |
CAY-10008846 |
|
|
|
The peroxisome
proliferator-activated receptors (PPARs) are lipid-activated
transcription factors often used as drug targets for the treatment of
metabolic disorders. CAY10573 is a PPAR agonist that displays potent
binding at PPARα, γ, and δ with IC50 values of 113, 50, and 223 nM,
respectively. It potently transactivates PPARα, γ, and δ with EC50
values of 8, 70, and 500 nM, respectively. CAY10573 demonstrates
stronger binding and functional activity for PPARγ than the antidiabetic
compound rosiglitazone (IC50 = 92 nM; EC50 = 220 nM). |
|
CAY10574 |
CAY-10011247 |
|
|
|
Cyclin-dependent
kinases (CDKs) play a key role in regulating cell division by
phosphorylating distinct substrates in different phases of the cell
cycle. Cell cycle deregulation in many cancers often results from
altered CDK activity. Thus, CDKs are potential pharmacological targets
for anticancer agents. CAY10574 is a potent, selective inhibitor of CDK9
in vitro with an IC50 value of 0.35 M. It is also a competitive
inhibitor of CDK2-cyclin E with respect to ATP, with Ki and IC50 values
of 13.3 and 20 M, respectively. CAY10574 reduces the population of
S-phase cells of the cancer cell line HT-29 and blocks proliferation of
several other cancer cell lines including MCF7, HOS, G361, and K562
cells with IC50 values of 33, 49, 64, and 62 M, respectively. |
|
CAY10575 |
CAY-10011248 |
|
|
|
The NF-kB/Rel
transcription factors, known to be involved in the regulation of
pro-inflammatory cytokines and the pathogenesis of a variety of
diseases, are present in the cytosol in an inactive state, complexed
with inhibitory IkB proteins. NF-kB is activated upon degradation of IkB
following IKK-a and IKK- phosphorylation. IKK-e, a homolog of IKK-a and
IKK-, can also activate NF-kB. IKK-e is expressed predominantly in
immune cells and is thought to play a role in the immune response.
CAY10575 is a benzimidazole analog that inhibits IKK-e with an IC50
value of ~15.8 M. |
|
CAY10576 |
CAY-10011249 |
|
|
|
CAY10576 is a
benzimidazole analog that selectively inhibits IKK-e with an IC50 value
of 40 nM and is essentially inactive at IKK-a and IKK-. |
|
CAY10577 |
CAY-10011256 |
|
|
|
Casein kinase-2 (CK2)
is a serine/threonine-selective protein kinase involved in many signal
transduction pathways. CK2 is known to negatively regulate apoptosis,
and its activity is increased in many proliferating tissues and tumors,
which lends promise as an anticancer drug target. CAY10577 inhibits CK2
with an IC50 value of 0.8 M. |
|
CAY10578 |
CAY-10011264 |
|
|
|
Casein Kinase-2 (CK2)
is a constitutive protein kinase involved in many signal transduction
pathways. CK2 is known to negatively regulate apoptosis, and its
activity is increased in many proliferating tissues and tumors, which
lends promise as an anticancer drug target. CAY10578 is a potent
inhibitor of CK2 with an IC50 value of 0.3 M. This compound is ATP
competitive, displaying a Ki value of 0.2 M and only minimally inhibits
the activities of other protein kinases (e.g., GSK3, CDK5, and MSK1). |
|
CAY10580 |
CAY-16835 |
|
|
|
Prostaglandin E2
(PGE2) activates four E prostanoid (EP) receptors, EP1-4. EP4 is a
Gs-protein coupled receptor that, by elevating the second messenger
cAMP, plays important roles in bone formation and resorption, cancer,
and atherosclerosis. CAY10580 is an 8-aza-11-dehydroxy saturated analog
of prostaglandin E2 (PGE2). It selectively binds the EP4 receptor (Ki =
35 nM) relative to the EP1, EP2, and EP3 receptors (Ki = 3,000, 2,000,
and >3,000 nM, respectively). CAY10580 stimulates cAMP formation in
excised murine ovaries. |
|
CAY10581 |
CAY-16838 |
|
|
|
The enzyme
indoleamine 2,3-dioxygenase (IDO) has been implicated in mediating
pathological immunosuppression associated with certain diseases,
including cancer. Several
naphthoquinones inhibit IDO in vitro and in cells, but at low (μM)
potency. Importantly,
naphthoquinones reduce tumor growth in wild type mice but not in
IDO-deficient mice. CAY10581 is a naphthoquinone derivative that
potently inhibits IDO (IC50 = 55 nM).
It is a more potent inhibitor of IDO than annulin B or
1-methyl-d-tryptophan (1MT). CAY10581 acts as a reversible uncompetitive
inhibitor of IDO and demonstrates minimal impact on cell viability at
100 μM after 24 hours. |
|
CAY10589 |
CAY-13164 |
|
|
|
CAY10589 is a dual
inhibitor of mPGES-1 (IC50 = 1.3 μM) and 5-LO (IC50 = 1.0 μM). It
effectively inhibits PGE2 and LT synthesis in both cell free and intact
cell assays. CAY10589 has minor effects on COX-1 and COX-2, inhibiting
these enzymes 34% and 38.8%, respectively, at 10 μM. |
|
CAY10592 |
CAY-10012536 |
|
|
|
Peroxisome
proliferator-activated receptors (PPARs) α, δ, γ are ligand-activated
nuclear transcription factors involved in the regulation of energy
homeostasis as well as insulin sensitivity and glucose metabolism.
Pharmacologies of PPARδ receptor agonists, though relatively obscure,
have recently been reported to elevate high-density lipoprotein (HDL)
cholesterol and lower plasma triglyceride (TG) levels in obese insulin
resistant rhesus monkeys. CAY10592 is a full PPARδ agonist (EC50 = 30
nM) in a fatty acid oxidation assay of rat L6 muscle cells with
desirable oral pharmacokinetic properties. In a transactivation assay
using human PPAR receptors, CAY10592 acts as a selective partial PPARδ
agonist (EC50 = 53 nM) with no effect on PPARα or PPARγ activity up to
30 M. Chronic treatment of high fat fed ApoB100/CETP-transgenic mice
with CAY10592 at a dose of 20 mg/kg increases HDL levels, decreases
low-density lipoprotein and TG levels, and improves insulin sensitivity. |
|
CAY10594 |
CAY-13207 |
|
|
|
CAY10594 is a potent
PLD2 inhibitor, both in vitro (IC50 = 140 nM) and in cells (IC50 = 110
nM). It is also effective as a PLD1 inhibitor at higher concentrations
(IC50 = 5.1 μM in vitro, 1.0 μM in cells). CAY10594 strongly inhibits
the invasive migration of breast cancer cells in transwell assays,
suggesting that PLD might be a useful target in blocking tumor cell
invasion. |
|
CAY10596 |
CAY-13216 |
|
|
|
CAY10596 is a
bicyclic cannabinoid analog that avidly binds the central cannabinoid
receptor (Ki = 0.83 nM) and shows high antinociceptive activity.
It is ten-fold more potent than ?9-tetrahydrocannabinol in
analgesic, motor depressant, anticonvulsant, and hypothermic effects in
mice. |
|
CAY10597 |
CAY-10012539 |
|
|
|
The biological
effects of prostaglandin D2 (PGD2) are transduced by at least two
7-transmembrane G protein-coupled receptors, designated DP1 and
CRTH2/DP2. In humans, CRTH2/DP2 is expressed on Th2 cells, eosinophils,
and basophils where it mediates the chemotactic activity of PGD2.
CAY10597 is a potent CRTH2/DP2 receptor antangonist that binds to the
human receptor with a Ki value of 37 nM. The R enantiomer is slightly
more potent exhibiting Ki values of 23 and 22 nM at the human and murine
CRTH2/DP2 receptor, respectively. The R enantiomer of CAY10597 inhibits
eosinophil chemotaxis induced by 13,14-dihydro-15-keto-PGD2 with an IC50
value of 40 nM. |
|
CAY10603 |
CAY-13146 |
|
|
|
CAY10603 is a potent
and selective inhibitor of HDAC6 (IC50 = 0.002 nM, as compared with 271,
252, 0.42, 6851, and 90.7 nM for HDACs 1, 2, 3, 8, and 10,
respectively). Also, CAY10603 prevents the growth of several pancreatic
cancer cell lines (IC50 = 0.1-1 μM). The HDAC6 inhibitor is more active
in inhibiting cell growth than the broad spectrum HDAC inhibitor
suberoylanilide hydroamic acid (SAHA). |
|
CBDD |
CAY-13285 |
|
|
|
CBDD is a cannabidiol
derivative that potently and selectively inhibits 15-LO with an IC50
value of 0.28 M. It does not inhibit 5-LO effectively (IC50
200 M). |
|
CBHA |
CAY-13172 |
|
|
|
CBHA is a potent HDAC
inhibitor, exhibiting ID50 values of 0.01 and 0.07 μM in vitro for HDAC1
and HDAC3, respectively. CBHA also induces apoptosis in nine different
neuroblastoma cell lines in culture (0.5-4.0 μM) and completely
suppresses neuroblastoma tumor growth in SCID mice at 200 mg/kg. The
efficacy of CBHA for suppressing tumor growth in mice is enhanced by the
addition of retinoic acid. |
|
CCT018159 |
CAY-10012591 |
|
|
|
The heat shock
protein 90 (Hsp90) is a molecular chaperone that activates and maintains
the biological functioning of several client proteins, many of which are
associated with oncogenic signaling pathways. Its activity is driven by
ATP and regulated by co-chaperones such as Hsp72. CCT018159 is a
3,4-diaryl pyrazoloresorcinol compound that inhibits the ATPase activity
of Hsp90 with IC50 values of 3.2 and 6.6 M for human Hsp90β and yeast
Hsp90, respectively. At concentrations up to 100 M, CCT018159 does not
inhibit human Hsp72 ATPase or topoisomerase II, yet at 50 M CCT018159
inhibits 13 out of a panel of 20 commonly studied kinases. In human
tumor xenografts, such as SKMEL 28 melanoma cells, CCT018159 induces
Hsp72 expression and decreases the expression of oncogenic client
proteins such as C-RAF, ERBB2, and CDK4. |
|
CD34 Monoclonal FITC
Antibody (Clone ICO-115) |
CAY-10208 |
|
|
|
This CD34 monoclonal
antibody recognizes an extracellular carbohydrate epitope of CD34. CD34
is a type I transmembrane glycoprotein (Mr = 104-120 kDa) expressed on
stem cells, early hematopoietic progenitor cells, bone marrow stroma
cells, endothelial cells, embryonic fibroblasts, and neurons. CD34
analysis can be used for the differential identification of acute
leukemias as well as routine analysis of cultured stem cell lines. |
|
CD4/CD8 Monoclonal
FITC/PE Antibody |
CAY-10009852 |
|
|
|
This antibody pair is
intended for the immunochemical detection of human CD4+ and CD8+ cells
by flow cytometry. Human whole blood samples may be stained directly
followed by red blood cell lysis with the provided reagents. CD4 and CD8
are each expressed on a variety of white blood cells. Therefore,
staining parallel samples or o-staining is recommended to identify
specific cell populations when using the CD4/CD8 antibody pair. For
example, confirm CD4+ or CD8+ T cells as those only expressing CD3. The
MHC class I and II molecules of antigen presenting cells specifically
interact with T cell receptor and co-receptors CD8 and CD4,
respectively. CD4 and CD8 are co-expressed on T cells during
development. However T cell maturation can result in distinct
populations of CD4+ (helper/suppressor) or CD8+ (cytotoxic) T cells
residing in the peripheral circulatory system. Peripheral CD4+ T cell
abundance is commonly employed for monitoring progression of HIV
infections and other immunosuppression. Evidence supports the existence
of arachidonic acid metabolites involved in immunosuppression, immune
cell maturation, differentiation, and chemotaxis. These events have been
implicated in chronic inflammation associated with the disease states
such as cancer and atherosclerosis. |
|
Chenodeoxycholic Acid |
CAY-10011286 |
|
|
|
Bile acids are
essential for solubilization and transport of dietary lipids, are the
major products of cholesterol catabolism, and are physiological ligands
for farnesoid X receptor (FXR), a nuclear receptor that regulates genes
involved in lipid metabolism. They are also inherently cytotoxic,
physiological imbalance contributes to increased oxidative stress. Bile
acid-controlled signaling pathways are promising novel targets to treat
such metabolic diseases as obesity, type II diabetes, hyperlipidemia,
and atherosclerosis. Chenodeoxycholic acis (CDCA) is a hydrophobic
primary bile acid that activates nuclear receptors involved in
cholesterol metabolism. EC50 concentrations for activation of FXR range
from 13 to 34 μM. In cells, CDCA also binds to bile acid binding
proteins (BABP) with a reported stiochiometery of 1:2. CDCA toxicity is
linked to increased cellular glutathione levels and increased oxidative
stress. Exposure of cells to excess CDCA contributes to liver and
intestinal cancers. |
|
cis-ACCP |
CAY-10012583 |
|
|
|
Matrix
metalloproteinases (MMPs) belong to a family of proteases that play a
crucial role in tissue remodeling and repair by degrading extracellular
matrix proteins, thus enabling cell migration. Overexpression of MMPs
are linked to diseases such as cancer, arthritis, osteoporosis, and
arteriosclerosis. cis-ACCP is a reversible and competitive inhibitor of
type IV collagen-specific MMP-2 and MMP-9 with preference towards MMP-2
(IC50 = and 20 M, respectively). At 100 M, cis-ACCP prevents 90% of
tumor cell invasion across matrigel-coated membranes in vitro. |
|
cis-Trismethoxy Resveratrol |
CAY-13199 |
|
|
|
Resveratrol is a
potent antioxidant found in grapes and red wine that also has
anti-proliferative, anti-neoplastic and anti-angiogenic activities.
In addition, resveratrol activates sirtuins and, in yeast,
extends lifespan. cis-Trismethoxy resveratrol is a potent anti-mitotic
drug that is 100-fold more active than resveratrol at inhibiting the
growth of human colon cancer Caco-2 cells.
It inhibits tubulin polymerization in a dose-dependent manner
(IC50 = 4 μM) and inhibits
enzymes involved in the synthesis of the polyamines, putrescine, and
spermidine. Trismethoxy
resveratrol has superior pharmacokinetic characteristics when compared
with resveratrol, including greater plasma exposure, longer elimination
half-life, and lower clearance. |
|
Clobenpropit (dihydrobromide) |
CAY-10011126 |
|
|
|
Clobenpropit
dihydrobromide is a selective histamine H3 receptor antagonist that
crosses the blood-brain barrier; inhibits histamine binding in rat brain
with an ED50 value of 10.5 mg/kg; protects cultured cortical neurons
from NMDA-induced excitotoxicity by stimulating GABA release; in mice
and rats protects against kindled seizures through its effects on
histamine and GABA. |
|
Clonazepam-d4 |
CAY-10010677 |
|
|
|
Clonazepam is an
anticonvulsant used for serveral types of seizures, including myotonic
or atonic seizures, photosensitive epilepsy, and absence seizures,
although tolerance amy develop. It is seldom effective in generalized
tonic-clonic or partial seizures. The mechanism of action appears to
involve the enhancement of γ-aminobutyric acid receptor responses. |
|
Clopidogrel-d3
hydrogen sulfate |
CAY-10010673 |
|
|
|
Clopidogrel is a
potent oral antiplatelet agent often used in the treatment of coronary
artery disease, peripheral vascular disease, and cerebrovascular
disease. The mechanism of action of clopidogrel is irreversible blockade
of the adenosine diphosphate (ADP) receptor on platelet cell membranes.
This receptor is named P2Y12 and is important in platelet aggregation,
the cross-linking of platelets by fibrin. The blockade of this receptor
inhibits platelet aggregation by blocking activation of the glycoprotein
IIb/IIIa pathway. |
|
COX Fluorescent
Activity Assay Kit |
CAY-700200 |
|
|
|
Cyclooxygenase (COX,
also called Prostaglandin H Synthase or PGHS) is a bifunctional enzyme
exhibiting both COX and peroxidase activities. The COX component
converts arachidonic acid to a hydroperoxy endoperoxide (PGG2), and the
peroxidase component reduces the endoperoxide to the corresponding
alcohol (PGH2), the precursor of PGs, thromboxanes, and
prostacyclins.1,2 It is now well established that there are two distinct
isoforms of COX, namely COX-1 and COX-2. Cayman's COX Fluorescent
Activity Assay provides a convenient fluorescence-based method for
detecting COX-1 or COX-2 activity in both crude (cell lysates/tissue
homogenates) and purified enzyme preparations. The assay utilizes the
peroxidase component of COXs. In this assay, the reaction between PGG2
and ADHP (10-acetyl-3,7-dihydroxyphenoxazine) produces the highly
fluorescent compound resorufin that can be analyzed using an excitation
wavelength of 530-540 nm and an emission wavelength of 585-595 nm. The
kit includes isozyme-specific
inhibitors for distinguishing COX-2 activity from COX-1 activity. |
|
CP 47,497 |
CAY-16851 |
|
|
|
CP 47,497 is a
monophenol cannabimimetic compound that binds the central cannabinoid
(CB1) receptor with a Ki value of 2.2 nM. It is equivalent in analgesic
potency to Δ9-THC and exhibits other CB biological activities as well. |
|
C-Reactive Protein
(human) EIA Kit |
CAY-10011236 |
|
|
|
C-Reactive Protein
(CRP) is a 224 amino acid protein that is synthesized primarily by
hepatocytes, and to a lesser extent adipocytes. CRP plasma levels
increase ~1,000-fold in response to acute and chronic inflammatory
conditions, making it a useful gauge of inflammation in a wide range of
physiological and pathological conditions. Normal levels of serum CRP
(0.64 g/ml) do not differ between healthy adult men and women, but tend
to increase slightly with age. High plasma CRP concentrations (>3 g/ml)
are associated with an increased risk for atherosclerosis. CRP has been
implicated as a contributor to atherogenesis by modulating endothelial
function, stimulating coagulation, inducing the expression of ICAM-1,
VCAM-1, and E-selectin, mediating uptake of LDL into macrophages, and
destabilizing plaques. In addition, CRP can bind in a calcium-dependent
manner to phosphocholine on microbes, act as a ligand for specific
receptors on phagocytic leukocytes, mediate activation of monocytes and
macrophages via IL-6, TNF-α and other cytokines, and assist in the
complement pathway. Caymans CRP (human) EIA Kit is an immunometric assay
which can be used to measure CRP in plasma without prior sample
purification. The standard curve spans the range of 0-3,000 pg/ml with a
limit of detection of approximately 50 pg/ml. |
|
Cysteinyl Leukotriene
Express EIA Kit |
CAY-10009291 |
|
|
|
Leukotrienes (LTs)
are a group of acute inflammatory mediators derived from arachidonic
acid via the 5-lipoxygenase (5-LO) pathway in leukocytes. LTC4, LTD4,
and LTE4 are collectively referred to as cysteinyl leukotrienes
(CysLTs). LTC4 and LTD4 are potent mediators of asthma and
hypersensitivity. They induce bronchoconstriction, increase
microvascular permeability, and are vasoconstrictors of coronary
arteries. The biological activity of LTE4 is much lower in most systems
studied, but its presence reflects the prior existence of LTC4 and LTD4.
Cayman's CysLT Express EIA Kit is a competitive assay that can be used
for measurement of all three primary CysLTs in urine, culture media, and
other sample matrices. The EIA typically displays an IC50 (50% B/B0) of
approximately 80 pg/ml and a detection limit (80% B/B0) of approximately
20 pg/ml. This sensitive assay takes about three hours to complete. |
|
Deoxynojirimycin Tetrabenzyl Ether |
CAY-10011914 |
|
|
|
Deoxynojirimycin (dNM) tetrabenzyl ether is an intermediate for the
synthesis of glucosylceramide synthase inhibitors such as 1-dNM, a
glucose analog that potently inhibits a-glucosidase I and II. |
|
D-erythro-Sphingosine C-20 |
CAY-10007903 |
|
|
|
Sphingosines are
long-chain base precursors of cellular sphingolipids used directly in
the synthesis of ceramide, which in combination with sialic acid forms
ganglioside. Sphingosine can exist in four stereoisomers, however only
D-erythro-sphingosine occurs naturally. Compared to other sphingolipids
throughout the body, which are predominantly composed of C-18
sphingosine, only central nervous system (CNS) gangliosides contain
significant amounts of D-erythro-sphingosine C-20.
The concentration of D-erythro-sphingosine C-20 within mammalian
brain gangliosides apparently increases with developmental maturation.
Furthermore, the ratio of C-18 to C-20 sphingosine in the brain is
thought to be related to some nervous system degeneration processes. |
|
Diallyl Trisulfide |
CAY-10012577 |
|
|
|
Hydrogen sulfide
(H2S) is an endogenously-produced gaseous second messenger that can
regulate many physiological processes. Diallyl trisulfide (DATS) is an
organic polysulfide compound found in garlic that acts as an H2S donor.
It reduces the survival of prostate cancer PC-3 cells (IC50 = 22 μM) and
inhibits the growth of human colon adenocarcinoma HCT-15 cells (IC50 =
11.5 μM). DATS suppresses the growth of PC-3 xenografts in vivo in mice
and induces vascular smooth muscle relaxation. Garlic extracts also
lower cholesterol and there is evidence that DATS can alter the
expression of genes and inhibit enzymes that are relevant to cholesterol
synthesis. |
|
Disuccinimidyl Suberate |
CAY-13008 |
|
|
|
Disuccinimidyl
suberate (DSS) is a bifunctional cross-linking reagent which contains
two N-hydroxysuccinimide esters that are reactive toward primary amines.
DSS is membrane-permeable and is commonly used to cross-link
proteins in intact cells. |
|
DL-Propargylglycine
(hydrochloride) |
CAY-10010948 |
|
|
|
Hydrogen sulphide
(H2S), a naturally occurring gasotransmitter, is a potent vasodilator
and pro-inflammatory mediator. DL-Propargylglycine (PAG) is an
irreversible inhibitor of the H2S synthesizing enzyme
cystathionine-?-lyase (CSE). PAG blocks H2S synthesis activity in rat
liver preparations with an IC50 value of 55 M and abolishes the rise in
plasma H2S in anaesthetized rats induced with hemorrhagic shock. At
concentrations ranging from 25-100 mg/kg, PAG can reduce H2S-associated
inflammation in rodent models of pancreatitis, oedema, and endotoxemia. |
|
D-myo-Inositol-1,3,4,6-tetraphosphate (ammonium salt) |
CAY-10008442 |
|
|
|
The inositol
phosphates are a family of molecules produced by altering the
phosphorylation status of each of the six carbons on the cyclic inositol
structure. They act as second
messengers, regulating a wide array of cellular functions.
D-myo-inositol-1,3,4,6-tetraphosphate(Ins(1,3,4,6)P4)
largely acts an intermediate, serving as substrate for
inositol-1,3,4,6-tetraphosphate 5-kinase to produce
inositol-1,3,4,5,6-pentaphosphate, or inositol-1,3,4,6-tetraphosphate
2-kinase to give inositol-1,2,3,4,6-pentaphosphate.
These inositol pentaphosphates can be further phosphorylated to
produce inositol-1,2,3,4,5,6-hexakisphosphate, or phytic acid, which
serves diverse roles in eukaryotic tissues. Ins(1,3,4,6)P4 is a poor
activator of the inositol 1,4,5-trisphospate receptor in vitro. Other
functions of this inositol phosphate remain to be elucidated. |
|
D-myo-Inositol-2,3,5-triphosphate (ammonium salt) |
CAY-10008423 |
|
|
|
D-myo-Inositol-2,3,5-triphosphate (ammonium salt) (Ins(2,3,5)P3
(ammonium salt)) is a member of the inositol phosphate (InsP) family of
second messengers that play a critical role in the transmission of
cellular signals. The most studied InsP, Ins(1,4,5)P3 is a second
messenger produced in cells by phospholipase C (PLC)-mediated hydrolysis
of phosphatidylinositol-4,5-biphosphate. Binding Ins(1,4,5)P3 to its
receptor on the endoplasmic reticulum results in opening of the calcium
channels and an increase in intracellular calcium. Ins(2,3,5)P3
(ammonium salt) (tested as a racemic mixture) is 500-fold less potent
than Ins(1,4,5)-P3 at initiating Ca2+ release when injected into Xenopus
oocytes. |
|
D-myo-Inositol-2,5,6-trisphosphate (sodium salt) |
CAY-10008424 |
|
|
|
Ins(2,5,6)P3 (sodium
salt) is a member of the inositol phosphate (InsP) family of second
messengers that play a critical role in the transmission of cellular
signals. The most studied InsP, Ins(1,4,5)P3 is a second messenger
produced in cells by phospholipase C (PLC)-mediated hydrolysis of
phosphatidylinositol-4,5-biphosphate. Binding of the Ins(1,4,5)P3 to its
receptor on the endoplasmic reticulum results in opening of calcium
channels and an increase in intracellular calcium. Ins(2,5,6)P3 is a
less potent inducer of calcium release from permeabilized rat basophilic
leukemia cells with an EC50 value of 110 M compared to Ins(1,4,5)P3,
which has an EC50 value of 0.17 M. |
|
Docosahexaenoic Acid ethyl ester |
CAY-9090310 |
|
|
|
Fish oils in the diet
have anti-inflammatory and cardiovascular benefits due to an abundance
of ω-3 polyunsaturated fatty acids (PUFAs), including docosahexaenoic
acid (DHA). DHA is the most abundant ω-3 PUFA in neural tissues,
especially in the retina and brain. DHA ethyl ester (DHA-EE) is the
stabilized ethyl ester form of the ω-3 22:6 fatty acid. Dietary intake
of DHA-EE enhances maze-learning ability in old mice. In rats, dietary
DHA-EE increases plasma and erythrocyte membrane DHA levels without
altering the content of the ω-6 arachidonic acid. Dietary DHA-EE
increases fatty acid oxidation enzymes in rats and, in humans with
peroxisomal disorders, improves vision, liver function, muscle tone and
social contact. The ω-3 fatty acid eicosapentaenoic acid (EPA)
competitively inhibits the metabolism of arachidonic acid by
cyclooxygenase enzymes, suggesting that DHA-EE may also directly
modulate the actions of enzymes involved in fatty acid metabolism. |
|
Docosahexaenoyl glycine |
CAY-9000328 |
|
|
|
The ω-3
polyunsaturated fatty acids (PUFAs) found in fish oils provide
cardiovascular benefits. Docosahexaenoic acid (DHA), a C22:6 PUFA, is
the most abundant ω-3 fatty acid in neural tissues, especially in the
retina and brain. It can be synthesized from other dietary ω-3 PUFAs or
taken as a nutritional supplement. Docosahexaenoyl glycine consists of
DHA with glycine attached at its carboxy terminus. |
|
Docosanoic acid |
CAY-9000338 |
|
|
|
Docosanoic acid is a
long-chain saturated fatty acid that exists naturally as a triglyceride
in canola, peanut, marine animal oils as well as animal milk fats and
peanut skins. Commercially, docosanoic acid is regularly used to give
hair conditioners and moisturizers their smoothing properties. As a
dietary oil, docosanoic acid has poor bioavailability in humans, yet
compared with oleic acid, docosanoic acid significantly raises serum
total and low-density lipoprotein-cholesterol concentrations. |
|
DPP (IV) Inhibitor
Screening Assay Kit |
CAY-700210 |
|
|
|
Caymans DPP (IV)
Inhibitor Screening Assay provides a convenient fluorescence-based
method for screening DPP (IV) inhibitors. The assay uses the fluorogenic
substrate, Gly-Pro-Aminomethylcoumarin (AMC), to measure DPP (IV)
activity. Cleavage of the peptide bond by DPP releases the free AMC
group, resulting in fluorescence that can be analyzed using an
excitation wavelength of 350-360 nm and an emission wavelength of
450-465 nm. |
|
Ebselen Oxide |
CAY-10012298 |
|
|
|
Ebselen is an
excellent scavenger of peroxynitrite and is used for the treatment of
cerebral infarctions. Ebselen oxide, formed by the oxidation of ebselen,
lacks antioxidant activity, indicating that it can serve as a negative
control for ebselen. |
|
Eicosadienoic Acid (5Z,14Z) |
CAY-10010484 |
|
|
|
Eicosadienoic acid (5Z,14Z) is a novel ω-6 C20:2 fatty acid. The more
common eicosadienoic acid 11Z,14Z) competitively inhibits inosine
5-monophosphate dehydrogenase (Ki = 3.1 M) and inhibits the binding of
LTB4 to its receptor on neutrophils (Ki = 3.0 M). Also, serum levels of
eicosadienoic acids negatively correlate with degree of sleep
disturbance. Eicosadienoic acids are converted by desaturases, in vivo,
to eicosatrienoic acids, which are potent vasodilators. The
physiological effects of eicosadienoic acid (5Z,14Z) are unstudied. |
|
Eicosadienoic Acid (8Z,14Z) |
CAY-16854 |
|
|
|
Eicosadienoic acid (8Z,14Z) is an ω-8 C20:2 fatty acid. The presence of
Eicosadienoic acid (8Z,14Z) has been detected in human milk at a level
of 0.19% (weight % total fatty acids). Eicosadienoic acids are converted
by desaturases, in vivo, to eicosatrienoic acids, which are potent
vasodilators. The physiological effects of eicosadienoic acid (8Z,14Z)
are unstudied. |
|
Eicosapentaenoic Acid Quant-PAK |
CAY-13048 |
|
|
|
The eicosapentaenoic
acid (EPA) Quant-PAK has been designed for the convenient, precise
quantification of EPA by GC- or LC-MS. It includes a 50 g vial of EPA-d5
and a precisely weighed vial of unlabeled EPA, with the precise weight
(2-4 mg) indicated on the vial. This unlabeled EPA can be used to
quantify the EPA-d5 standard by constructing a standard curve of peak
intensity ratios (deuterated versus unlabeled). |
|
Elesclomol |
CAY-10011192 |
|
|
|
Elesclomol is a
pro-apoptotic agent that demonstrates anti-tumor activity against a
broad range of cancer cell types. It promotes apoptosis in Hs294T
melanoma cells treated with 100 nmol/L for six hours by rapidly
generating reactive oxygen species and inducing the transcription of
Hsp70 and metallothionein. Stage III clinical trials to assess efficacy
of elesclomol treatment in combination with paclitaxel in patients with
stage IV metastatic melanoma were suspended due to safety concerns. |
|
ent-8-iso
Prostaglandin F2.alpha.-d9 |
CAY-10011721 |
|
|
|
Isoprostanes are
produced by the non-enzymatic, free-radical peroxidation of arachidonic
acid. They have been used as biomarkers of oxidative stress, but they
also have been found to have a potent biological activity. ent-8-iso
Prostaglandin F2α (ent-8-iso PGF2α) is a potent vasoconstrictor of
porcine retinal and brain microvessels with EC50 values of 31 and 54 nM,
respectively. |
|
Epoxomicin |
CAY-10007806 |
|
|
|
Epoximicin is a
potent anti-tumor agent isolated from Actinomycetes that is used as a
selective and irreversible inhibitor of the 20S proteasome. It inhibits
proteasome activity in cell growth assays with an IC50 value of 4 nM and
demonstrates potent cytotoxicity against B16-F10, HCT116, and Moser
solid tumor cells, as well as P388 and K562 leukemia cells with IC50
values ranging from 2-44 nM. By inhibiting osteoblast proteasome
activity, epoximicin stimulates bone formation at concentrations as low
as 10 nM. Intraperitoneal injection of 1.5 mg/kg epoximicin given daily
for two weeks induces Parkinsons-like symptoms in rats and addition of
100 nM epoximicin to rat ventral midbrain cultures results in apoptosis
specific to dopaminergic neurons. Epoximicin-induced parkinsonism can be
a useful model to examine mechanisms and therapies for the disease. |
|
Erythropoietin
Western Ready Control |
CAY-10009989 |
|
|
|
Erythropietin (EPO)
is a glycoprotein hormone that is the primary regulator of
erythropoiesis, maintaining the bodys red blood cell mass at an optimum
level. In response to a decrease in tissue oxygenation, EPO protein
levels are upregulated in the kidney. The secreted hormone binds to
specific receptors on the surface of red blood cell precursors in the
bone marrow, leading to their survival, proliferation, differentiation,
and ultimately to an increase in hematocrit. |
|
Ethyl-2,4-Dimethylthiazole-5-Carboxylate |
CAY-13232 |
|
|
|
Ethyl-2,4-dimethylthiazole-5-carboxylate is a highly functionalized and
biased thiazole used for drug discovery. It is used as a heterocyclic
building block to specifically modify lead compounds. |
|
Ethyl-L-NIO (hydrochloride) |
CAY-10012088 |
|
|
|
Ethyl-L-NIO, the
saturated analog of vinyl-L-NIO, is a modestly selective NOS inhibitor.
The Ki values for inhibition of nNOS, eNOS, and iNOS by ethyl-L-NIO are
5.3, 18, and 12 M, respectively, as determined using initial rate
measurements. However when evaluating the Ki/Km ratio, ethyl-L-NIO does
not show biologically significant selectivity for nNOS over eNOS, and
instead favors iNOS (Ki/Km = 3.79, 5, and 0.96 M, respectively).
Although ethyl-L-NIO inhibits nNOS, it does not inactivate nNOS in the
presence of NADPH and O2. |
|
EUK 118 |
CAY-10271 |
|
|
|
EUK 8 and EUK 134 are
synthetic catalytic scavengers of reactive oxygen species with
superoxide dismutase (SOD) and catalase mimetic activity. EUK 118 is a
structural analog of EUK 8 and EUK 134 with significantly reduced
activity. EUK 118 exhibits a catalase activity of 35 M O2 formed/minute
from 10 mM hydrogen peroxide, which is more than four times lower that
that observed for EUK 8 under the same conditions. Superoxide-mediated
reduction of an electron acceptor (i.e., SOD mimetic activity) was
inhibited by EUK 118 and EUK 8 with IC50 values of 2 and 0.7 M,
respectively. EUK 118 did not protect human dermal fibroblasts against
hydrogen peroxide-induced cell death. |
|
EUK 124 |
CAY-12500 |
|
|
|
EUK 8 and EUK 134 are
synthetic catalytic scavengers of reactive oxygen species with
superoxide dismutase (SOD) and catalase mimetic activity. EUK 124 is a
structural analog of EUK 8 and EUK 134 with significantly reduced
activity. EUK 124 and EUK 8 inhibit superoxide-mediated reduction of an
electron acceptor (i.e. SOD mimetic activity), with IC50 values of 5 M
and 0.7 M, respectively. |
|
FAAH Inhibitor
Screening Assay Kit |
CAY-10005196 |
|
|
|
The endocannabinoid
system is a ubiquitous lipid signaling system involved in various
regulatory functions throughout the body. The primary endocannabinoids,
arachidonoylethanolamide (AEA) and 2-arachidonoyl glycerol (2-AG), are
released upon demand from lipid precursors and bind to cannabinoid (CB1)
receptors in the brain or CB2 receptors in the peripheral tissues. Fatty
acid amide hydrolase (FAAH) is a cytosolic serine hydrolase responsible
for the degradation of fatty acid amides, including AEA. Finding
inhibitors to FAAH could offer a beneficial approach toward the
treatment of pain, obesity, and various neurological diseases where
higher endocannabinoid activity would be beneficial. Cayman's FAAH
Inhibitor Screening Assay Kit provides a convenient fluorescence-based
method for screening FAAH inhibitors. FAAH hydrolyzes AMC-arachidonoyl
amide resulting in the release of the fluorescent product,
7-amino-4-methylcoumarin (AMC). The fluorophore can be easily analyzed
using an excitation wavelength of 340-360 nm and an emission wavelength
of 450-465 nm. |
|
FABP2 (human recombinant) |
CAY-10009548 |
|
|
|
Fatty acid binding
protein 2 (FABP2) is one of nine known cytosolic FABPs ranging in size
from 14-15 kDa containing 127-132 amino acids. Members of this protein
family exhibit high-affinity for small lipophilic ligands and were named
according to the tissue from which they were initially isolated. Studies
suggest that FABPs are involved in the uptake and metabolism of fatty
acids, in the maintenance of cellular membrane fatty acid levels, in
intracellular trafficking of these substrates, in the modulation of
specific enzymes of lipid metabolic pathways, and in the modulation of
cell growth and differentiation. FABP family members have highly
conserved three dimensional structures and 22-73% amino acid sequence
similarity. FABP2 is composed of ten antiparallel b strands that form a
barrel and binds the ligand in a bent confirmation. It is exclusively
expressed in the intestinal enterocytes and is potentially a plasma
marker for intestinal injury. FABP2 polymorphism has been suggested to
be associated with gender specific obesity and increased risk of
diabetes. |
|
FABP3 Monoclonal
Antibody (Clone CC68) |
CAY-10233 |
|
|
|
Fatty acid binding
protein 3 (FABP3) is one of nine known cytosolic FABPs ranging in size
from 14-15 kDa containing 127-132 amino acids. Members of this protein
family exhibit high affinity for small lipophilic ligands and were named
according to the tissue from which they were initially isolated. Studies
suggest that FABPs are involved in the uptake and metabolism of fatty
acids, in the maintenance of cellular membrane fatty acid levels, in
intracellular trafficking of these substrates, in the modulation of
specific enzymes of lipid metabolic pathways, and in the modulation of
cell growth and differentiation. FABP family members have highly
conserved three dimensional structures and 22-73% amino acid sequence
similarity. FABP3 is composed of ten antiparallel β strands that form a
barrel and is the most widely distributed FABP. It is found in heart,
skeletal and smooth muscle, mammary epithelial cells, aorta, distal
tubules of the kidney, lung, brain, placenta, and ovary. FABP3 is a
potential biomarker for myocardial injury, especially for early
detection of acute myocardial infarction (AMI). |
|
Farnesyl
Thiosalicylic Acid Amide |
CAY-13175 |
|
|
|
Association of Ras
protein with the inner surface of the plasma membrane is required for
Ras signaling activity. Farnesyl thiosalicylic acid (FTS) is an
inhibitor of Ras-mediated signaling that functions by dislodging Ras
from the cell membrane thereby rendering it susceptible to proteolytic
degradation. FTS amide is an FTS derivative with an amide added to the
carboxyl group. FTS amide inhibits the growth of Panc-1 and U87 tumor
cells with IC50 values of 20 and 10 M, respectively, a relatively higher
potency compared to that of FTS (IC50s = 35 and 50 M, respectively).
Treatment of nude mice bearing either U87 glioblastoma or Panc-1 tumors
with 100 mg/kg FTS-amide twice daily for four days inhibits tumor growth
by at least 50% of controls. |
|
Fatty Acid Amide
Hydrolase (human recombinant) |
CAY-10010183 |
|
|
|
The endocannabinoid
system is a ubiquitous lipid signaling system that is involved in
various regulatory functions throughout the body. The main
endocannabinoids are arachidonoyl ethanolamide (AEA) and 2-arachidonoyl
glycerol (2-AG). They bind to G protein-coupled receptors, of which the
central cannabinoid (CB1) receptor is densely distributed in areas of
the brain related to motor control, cognition, emotional responses, and
homeostasis. Acting via the peripheral cannabinoid (CB2) receptor in the
peripheral tissues, the endocannabinoid system is one of the crucial
modulators of the autonomic nervous system, the immune system, and
microcirculation. Endocannabinoids are released upon demand from lipid
precursors in a receptor-dependent manner. They are transported into
cells by an apparently specific uptake system and degraded primarily by
two enzymes, fatty acid amide hydrolase (FAAH) and monoacylglycerol
lipase (MAGL), resulting in the termination of their biological actions.
FAAH, a serine hydrolase, can degrade many fatty acid amides, including
AEA. Although FAAH can hydrolyze 2-AG, the main enzyme responsible for
the inactivation of this monoglyceride is another serine hydrolase,
MAGL. Finding inhibitors to these endocannabinoid hydrolases could offer
another approach in the treatment of pain, obesity, and various
neurological diseases, where higher endocannabinoid activity would be
beneficial. An advantage of such enzyme inhibition over direct
cannabinoid agonists could result in higher selectivity, as it would
increase activity of the endocannabinoid system only at sites where
on-going production of endocannabinoids is taking place. |
|
Felodipine-d3 |
CAY-10010654 |
|
|
|
Felodipine is a
dihydropyridine calcium antagonist with positive inotropic effects. It
lowers blood pressure by reducing peripheral vascular resistance through
a highly selective action on smooth muscle in arteriolar reistance
vessels. |
|
Fluorescent Thiol Probe |
CAY-13083 |
|
|
|
The rapid, selective,
and sensitive sensing of thiols is important in diverse areas of
research. This fluorescent thiol probe responds upon exposure to thiols
with an increase in fluorescence intensity of up to 120-fold. The
response is selective for thiols and occurs in aqueous media. In the
absence of thiols, the probe is essentially non-fluorescent; thiols
cause cleavage of the probe, generating a fluorophore with an absorption
maximum of 563 nm and emission at 623 nm. The fluorescence quantum yield
of the cleaved product, generated in response to thiols, increases in
more viscous media, suggesting ideal performance in biological systems
and applicability to single-molecule or 2-photon sensing schemes. The
fluorescent thiol probe is
cell-permeable and reacts selectively with intracellular thiols. The
pseudo-first order rate constant (kobs) depends on substrate (e.g., 2.1
x 10-3 s-1 for cysteine, 2.0 x 10-5 s-1 for human serum albumin). |
|
FTY720 (R)-Phosphate |
CAY-10006407 |
|
|
|
FTY720 (R)-phosphate
is one of the stereoisomers of FTY720-phosphate, but it is apparently
not formed in vivo. FTY720 (S)-phosphate exhibits Ki values of 2.1, 5.9,
23, and 2.2 nM for S1P1,3,4,5, respectively, whereas the R isomer binds
with 5-130-fold lower affinity. |
|
FTY720 (S)-Phosphate |
CAY-10006408 |
|
|
|
FTY720 (S)-phosphate
is the single stereoisomer formed by phosphorylation of FTY720 in vivo,
as determined in rats and humans. It exhibits Ki values of 2.1, 5.9, 23,
and 2.2 nM for S1P1-5, respectively, whereas the R enantiomer binds with
5-130-fold lower affinity. FTY720 (S)-phosphate causes internalization
of S1P1 on lymphocytes, abrogating S1P-dependent egress of lymphocytes
from lymphoid organs. It also
enhances endothelial barrier function, stimulates the activity of the
sphingosine transporter Abcb1 and the leukotriene C4 transporter Abcc1
and inhibits cytosolic phospholipase A2 activity. |
|
Fulvestrant |
CAY-10011269 |
|
|
|
Fulvestrant is a
potent estrogen receptor (ER) antagonist that works by down-regulating
and degrading the estrogen receptor, ERα. The prescription drug,
Faslodex, is efficacious in the treatment of estrogen-sensitive breast
cancer, in part because it largely lacks agonist activity in relevant
tissues. However, fulvestrant was found to fully activate ER on rat
hippocampal neurons, suggesting it might afford protective neurological
benefits with aging. |
|
Glutathione
S-Transferase Polyclonal FITC Antibody |
CAY-10197 |
|
|
|
Caymans Glutathione
S-Transferase (GST) Polyclonal FITC Antibody may be used to monitor
espression of recombinant proteins tagged with GST (GST fusion
proteins). A recombinant GST-tagged protein is expected to migrate 26
kDa slower than the non-tagged version in reducing conditions on
SDS-PAGE. In general, GSTs are ubiquitous multifunctional enzymes, which
play a key role in cellular detoxification and researchers routinely
utilize the enzyme as a method to simplify the purification of
recombinant proteins. |
|
Glycerol Cell-Based Assay Kit |
CAY-10011725 |
|
|
|
In mammals,
triglycerides are constantly synthesized from fatty acids and segregated
into cytosolic lipid droplets, mainly in adipocytes, as the major energy
storage depot. During fasting, triglycerides stored in adipose tissue
and liver are hydrolyzed by hormone-sensitive lipase and adipose
triglyceride lipase to produce free fatty acids and glycerol.
Triglyceride/fatty acid cycling is a highly regulated process important
in metabolic regulation and heat production. Caymans Cell-Based Assay
Kit provides a convenient tool for studying triglycerides/fatty acid
cycling and its regulation in adipocytes or hepatocytes. This kit will
allow investigators to screen compounds involved in lipid storage and
metabolism. Chloroquine is included in the kit as a positive control for
screening pharmaceuticals that induce lipid droplet accumulation and
free glycerol release from hepatocytes. |
|
Glycerophospho-N-Arachidonoyl Ethanolamine |
CAY-10011347 |
|
|
|
N-Acylated
ethanolamines (NAE) are naturally-occurring lipids that have diverse
bioactivities. The different
types of NAE can be derived from glycerophospho-linked precursors by the
activity of glycerophosphodiesterase 1 (GDE1).
Glycerophospho-N-arachidonoyl ethanolamine is the precursor of
arachidonoyl ethanolamide (AEA), also known as anandamide.
AEA is an endogenous cannabinoid neurotransmitter that binds to
both central cannabinoid (CB1) and peripheral cannabinoid (CB2)
receptors. It inhibits the
specific binding of [3H]-HU-243 to synaptosomal membranes with a Ki
value of 52 nM, compared to 46 nM for Δ9-THC. |
|
Glycerophospho-N-Oleoyl Ethanolamine |
CAY-10011357 |
|
|
|
N-Acylated
ethanolamines (NAE) are naturally-occurring lipids that have diverse
bioactivities. For example, arachidonoyl ethanolamide (AEA) is an
endogenous cannabinoid neurotransmitter that evokes cellular responses
by activating the cannabinoid receptors, central cannabinoid (CB1) and
peripheral cannabinoid (CB2). The different types of NAE are derived
from glycerophospho-linked precursors by the activity of
glycerophosphodiesterase 1 (GDE1). Glycerophospho-N-oleoyl ethanolamine
is the precursor of oleoyl ethanolamide (OEA). OEA is an endogenous,
potent agonist for PPARα, exhibiting an EC50 value of 120 nM in a
transactivation assay. Systemic administration of OEA suppresses food
intake and reduces weight gain in rats (10 mg/kg intraperitoneally) and
PPARα wild type mice, but not in PPARα knockout mice. Like AEA, OEA is
metabolized by fatty acid amide hydrolase (FAAH). |
|
Glycerophospho-N-Palmitoyl Ethanolamine |
CAY-10011356 |
|
|
|
N-Acylated
ethanolamines (NAE) are naturally-occurring lipids that have diverse
bioactivities. For example, arachidonoyl ethanolamide (AEA) is an
endogenous neurotransmitter that evokes cellular responses by activating
the cannabinoid receptors, central cannabinoid (CB1) and peripheral
cannabinoid (CB2). The different types of NAE are derived from
glycerophospho-linked precursors by the activity of
glycerophosphodiesterase 1 (GDE1). Glycerophospho-N-palmitoyl
ethanolamine (GP-NPEA) is the metabolic precursor of palmitoyl
ethanolamide (PEA). PEA is an endogenous CB found in brain, liver, and
other mammalian tissues, that has potent anti-inflammatory activity in
vivo. PEA has low affinity for CB2 and no appreciable affinity for CB1,
suggesting that its efficacy is through a different receptor. |
|
GX15-070 (hydrochloride) |
CAY-10011180 |
|
|
|
Members of the Bcl-2
family of proteins are critical regulators of apoptosis by either
inhibiting or promoting cell death and are involved in a number of
cancers such as melanoma, breast, prostate, and lung carcinomas. The
pro-survival members, Bcl-2, Bcl-xL, Bcl-w, Mcl-1, and A1, are thought
to confer resistance to apoptosis in such circumstances by antagonizing
mitochondrial membrane permeabilization. GX15-070 is a pan Bcl-2
inhibitor that induces Bax- and Bak-mediated apoptosis by inhibiting
Bcl-2 protein-protein interactions (Ki = 220 nM for binding cytosolic
Bcl-2). GX15-070 at 1 M potently inhibits survival of murine E-Myc
lymphoma cells overexpressing either Mcl-1, Bcl-2, or A1. At 2 mg/kg
given once every three days, GX15-070 reduces tumor size in mice bearing
tumors derived from cervical (C33A), prostate (PC3), colon (SW480), or
mammary (4T1) carcinoma cells. GX15-070 is currently undergoing phase II
clinical evaluation for treatment of leukemia, lymphoma, and
solid tumor malignancies. |
|
HA-1077 (hydrochloride) |
CAY-10010559 |
|
|
|
Rho-kinase, an
effector of the small GTP-binding protein Rho, plays an important role
in various cellular functions including vascular smooth muscle
contraction, proliferation, and migration as well as inflammatory cell
mobility. HA-1077 is a potent inhibitor of Rho-associated Kinase II
(ROCK-II) and additionally inhibits Protein Kinase C-related Kinase 2
(PRK2), Mitogen- and Stress-Activated Protein Kinase (MSK1), and Mitogen
Activated Protein Kinase-Activated Protein Kinase 1b (MAPKAP-K1b) with
IC50 values of 1.9, 4, 5, and 15 M, respectively. By inhibiting the
activity of Rho-kinase, HA-1077 has been shown to reduce blood vessel
constriction, decrease pulmonary arterial pressure, inhibit tumor
angiogenesis, and improve insulin signaling in various rodent models.
While originally marketed for the prevention of cerebral vasospasm in
patients with subarachnoid hemorrhage, oral formulations of HA-1077 are
used for the treatment of a wide range of cardiovascular diseases
including pulmonary arterial hypertension and stable angina. |
|
Halopemide |
CAY-13205 |
|
|
|
Halopemide is a
potent inhibitor of phospholipase D (PLD), inhibiting human PLD1 and
PLD2 in vitro (IC50 = 220 and 310 nM, respectively) and PLD activity in
cells. Previously, halopemide has been found to inhibit dopamine
receptors and was evaluated as a neuroleptic agent. |
|
HDAC8 Inhibitor
Screening Assay Kit |
CAY-700230 |
|
|
|
Caymans HDAC8
Inhibitor Screening Assay provides a convenient fluorescence-based
method for screening HDAC8 inhibitors. The procedure requires only two
easy steps, both performed in the same microplate. In the first step,
the substrate, which comprises the p53 sequence
Arg-His-Lys-Lys(ε-acetyl)-AMC, is incubated with human recombinant
HDAC8. Deacetylation sensitizes the substrate such that treatment with
the developer in the second step releases a fluorescent product.
Fluorescence is then analyzed with an excitation wavelength of 350-360
nm and an emission wavelength of 450-465 nm. |
|
Heptacosadiene (7Z,11Z) |
CAY-10012567 |
|
|
|
The mating and social
behaviors of insects are largely orchestrated by a suite of volatile
cuticular hydrocarbon pheromones. 7(Z),11(Z)-Heptacosadiene is the
predominant female-specific courtship pheromone of the fruit fly D.
melanogaster. At concentrations above 100 ng, 7(Z),11(Z)-heptacosadiene
elicits wing vibrations in male D. melanogaster flies in a
dose-dependent manner. |
|
Hexadecanal-d5 |
CAY-16834 |
|
|
|
Sphingosine-1-phosphate (S1P) is a potent bioactive phospholipid that
exhibits a broad spectrum of biological activities including cell
proliferation, survival, migration, cytoskeletal organization, and
morphogenesis. Hexadecanal is the 16-carbon aldehyde analog of palmitic
acid. It is produced from the irreversible cleavage of S1P by S1P lyase
1 and is a major component of plasmalogen. |
|
HIF-1.alpha. Inhibitor |
CAY-10012682 |
|
|
|
Hypoxia inducible
factor-1 (HIF-1) is a heterodimeric transcription factor composed of a
HIF-1α subunit and HIF-1β subunit. Whereas the HIF-1β subunit is
constitutively expressed, the HIF-1α subunit is regulated by cellular
oxygen levels and therefore plays an important role in maintaining
cellular oxygen homeostasis. Under normoxic conditions, HIF-1α is
selectively hydroxylated on proline residues 402 and 577 and targeted
for destruction by the ubiquitin-proteasome system. Under hypoxic
conditions, HIF-1α accumulates and dimerizes with HIF-1β to promote the
transcription of a number of genes involved in angiogenesis, glycolysis,
growth factor signaling, tumor invasion, and metastasis. HIF-1α
inhibitor is a novel small molecule inhibitor of HIF-1α accumulation and
gene transcriptional activity. In a gene reporter assay using human
Hep3B and AGS cell lines, HIF-1α inhibitor prevented HIF-1
transcriptional activity with IC50 values of 2.6 and 0.7 M,
respectively. It blocks HIF-1α accumulation in Hep3B cells in a
concentration and time-dependent manner, with complete inhibition at a
concentration of 30 M within 12 hours. HIF-1α inhibitor also
significantly suppresses transcription of the HIF-1 target genes VEGF
and erythropoietin at 10 M. |
|
His-Express Detection EIA Kit |
CAY-10012445 |
|
|
|
Recombinant proteins
are routinely labeled with affinity tags, such as hexahistidine.
Cayman's His-Express Detection EIA Kit is competitive assay designed for
the rapid, semi-quantitative screening of cell lysates and affinity
column eludes for His-tagged proteins. It is intended to serve as a
substitute for SDS-PAGE, thereby expediting the screening of affinity
column fractions. |
|
Hydrochlorothiazide-d2,15N2 |
CAY-10010676 |
|
|
|
Hydrochlorothiazide
is a thiazide diuretic often considered the prototypical member of this
class. It reduces the reabsorption of electrolytes, including sodium,
potassium, chloride, and magnesium. It has been used in the treatment of
several disorders including edema, hypertension, diabetes insipidus, and
hypoparathyroidism. |
|
Hydrogen Peroxide
Cell-Based Assay Kit |
CAY-600050 |
|
|
|
Hydrogen peroxide
(H2O2) is a natural by-product of oxygen metabolism. It has strong
oxidizing capacity and is thus considered a highly reactive oxygen
species. It is well established that H2O2 is a cytotoxic agent but
evidence also suggests that H2O2 may be an important regulator of
eukaryotic signal transduction. Cayman's H2O2 Cell-Based Assay Kit
provides a simple fluorometric method for the sensitive quantitation of
H2O2 in cultured cells. H2O2 is detected using
10-acetyl-3,7-dihydroxyphenoxazine (ADHP), a highly sensitive and stable
probe for H2O2. In the presence of horseradish peroxidase, ADHP reacts
with H2O2 with a 1:1 stoichiometry to produce highly fluorescent
resorufin (excitation = 530-560 nm; emission = 590 nm). Catalase, an
H2O2 scavenger, is included in the kit for checking specificity of the
assay. |
|
Hydroxy Bupropion-d9 |
CAY-10010669 |
|
|
|
Bupropion is a
unicyclic, aminoketone antidepressent. The mechanism of its therapeutic
actions is not well understood, but it does appear to block dopamine
uptake. The hydrochloride is available as an aid to smoking cessation
treatment. |
|
Hydroxymetronidazole-d4 |
CAY-10010651 |
|
|
|
Metronidazole is a
nitroimidazole used to treat Amebiasis, Vaginitis, Trichomonas
infections, Giardiasis, Anaerobic bacteria, and Treponemal infections.
It has also been proposed as a radiation sensitizer for hypoxic cells.
According to the Fouth Annual Report on Carcinogens (NTP 85-002, 1985,
p133), this substance may reasonably be anticipated to be a carcinogen.
Metronidazole is a prodrug. It is converted in anaerobic organisms by
the redox enzyme pyruvate-ferredoxin oxidoreductase. The nitro group of
metronidazole is chemically reduced by ferredoxin (or a
ferredoxin-linked metabolic process) and the products are responsible
for disrupting the DNA helical structure, thus inhibiting nucleic acid
synthesis. |
|
IDFP |
CAY-10215 |
|
|
|
The endocannabinoids,
2-arachidonoyl glycerol (2-AG) and arachidonoyl ethanolamide (AEA), are
biologically active lipids that regulate diverse neurological and
metabolic functions by activating the cannabinoid receptors, central
cannabinoid (CB1) and peripheral cannabinoid (CB2). Monoacylglycerol
lipase (MAGL) and fatty acid amide hydrolase (FAAH) hydrolyze 2-AG and
AEA, respectively, thus terminating their biological function. IDFP is
an organophosphorus compound that dually inhibits MAGL and FAAH with
IC50 values of 0.8 and 3 nM, respectively. At 10 mg/kg, IDFP elevates
brain levels of 2-AG and AEA more than 10-fold, and decreases levels of
arachidonic acid by a similar magnitude. |
|
Imatinib (mesylate) |
CAY-13139 |
|
|
|
Imatinib mesylate is
a first generation tyrosine kinase inhibitor that is used in the
treatment of chronic myelogenous leukemia (CML), gastrointestinal
stromal tumors (GIST), and other cancers. It selectively targets certain
tyrosine kinases, including c-ABL, platelet-derived growth factor
receptor, and KIT. In CML, imatinib mesylate inhibits the oncoprotein
BCR-ABL, the product of the Philadelphia chromosome gene fusion. |
|
In Vitro Angiogenesis Assay Kit |
CAY-10009964 |
|
|
|
Angiogenesis is a
physiological process that occurs during wound healing and normal
development which involves the
growth of new blood vessels from pre-existing vessels. While normal
angiogenesis is critical for homeostasis, abnormal angiogenesis is an
important component of several diseases, most notably cancer where it is
essential for tumor development and metastasis. Therefore inhibition of
angiogenesis is one of the main therapeutic targets in cancer drug
discovery. Caymans In Vitro Angiogenesis Assay Kit uses a one-step model
to study regulators of angiogenesis. Cell survival is improved compared
to the other assays by use of a modified extracellular matrix that has
been validated in both short-term (2-3 days) and long-term (up to ten
days) experiments. Caymans kit includes PMA and JNJ-10198409 as controls
for stimulation and inhibition of angiogenesis, respectively, as well as
the fluorescent dye Calcein AM for visualization of cell organization.
This assay can be readily adapted to high throughput screening programs
for identifying angiogenesis inhibitors. |
|
Janex-1 |
CAY-10011246 |
|
|
|
Janus kinase 3 (JAK3)
is a cytoplasmic protein tyrosine kinase that functions in the
initiation of cytokine-triggered signal transduction by catalyzing the
phosphorylation of signal transduction and activators of transcription
(STATs). JAK3 is abundantly expressed in normal lymphoid cells as well
as human lymphoblastic and myeloblastic leukemia cells. Janex 1
selectively inhibits the tyrosine kinase activity of JAK3 with an
IC50 value of 78 M without affecting the enzymatic activity of JAK1,
JAK2, or other protein tyrosine kinases (IC50 > 350 M). Janex 1 induces
apoptosis in JAK3-expressing human leukemia cell lines NALM-6 and
LC1;19, but not in melanoma or squamous carcinoma cell lines. |
|
Jasmonic Acid |
CAY-88300 |
|
|
|
Jasmonic acid,
derived from linoleic acid, is a plant growth regulator involved in the
signaling mechanisms for a variety of conditions including plant
defense, wound healing, tuberization, fruit ripening, and senescence. |
|
JMV3002 |
CAY-10012699 |
|
|
|
Ghrelin is an
endogenous ligand for the growth hormone secretagogue receptor that
stimulates food intake and transduces signals to hypothalamic regulatory
nuclei that control energy homeostasis. JMV3002 is a potent ghrelin
receptor antagonist with an IC50 value of 1.1 nM in vitro. At 80 g/kg,
JMV3002 inhibits hexarelin-stimulated food intake by as much as 98% in
rats. JMV3002 alone does not elicit growth hormone release nor does it
inhibit hexarelin-stimulated growth hormone secretion when tested in
infant rats at a dose of 160 g/kg. |
|
JWH 018 |
CAY-13169 |
|
|
|
JWH 018 is a mildly
selective agonist of the peripheral cannabinoid (CB2) receptor, derived
from the aminoalkylindole WIN 55,212-2. The Ki values for binding
central cannabinoid (CB1) and CB2 receptors are 9.0 and 2.94 nM,
respectively, for a CB1:CB2 ratio of 3.06. Its effects on suppression of
spontaneous activity, maximum possible antinociceptive effect in the
tail-flick assay, and rectal temperature are comparable to those of WIN
55,212-2 when tested in rats. |
|
JWH 073 |
CAY-13170 |
|
|
|
JWH 073 is a mildly
selective agonist of the central cannabinoid (CB1) receptor derived from
the aminoalkylindole WIN 55,212-2. The Ki values for binding CB1 and the
peripheral cannabinoid (CB2) receptor are 8.9 and 38 nM, respectively
for a CB1:CB2 ratio of 0.23. Its effects on suppression of spontaneous
activity, maximum possible antinociceptive effect in the tail-flick
assay, and rectal temperature are comparable to those of WIN 55,212-2
when tested in rats. |
|
JWH 200 |
CAY-13171 |
|
|
|
JWH 200 is an
aminoalkylindole that acts as a cannabinoid (CB) receptor ligand.
It binds to the CB1
receptor with high-affinity (IC50 = 7.8-42 nM). The effects of JWH 200
in locomotor activity, tail-flick latency, hypothermia, and
ring-immobility tests are comparable or superior to Δ9-THC or
WIN-55,212. It potently inhibits
the contraction of electrically-stimulated murine vas deferens (IC50 =
3.7-6.0 nM). |
|
JZL184 |
CAY-13158 |
|
|
|
Endocannabinoids such
as 2-arachidonoyl glycerol (2-AG) and arachidonoyl ethanolamide (AEA)
are biologically active lipids that are involved in a number of synaptic
processes including activation of cannabinoid receptors.
Monoacylglycerol lipase (MAGL) is a serine hydrolase responsible for the
hydrolysis of 2-AG to arachidonic acid and glycerol, thus terminating
its biological function. JZL184 is a potent and selective inhibitor of
MAGL that displays IC50 values of 8 nM and 4 M for inhibition of MAGL
and fatty acid amide hydrolase in murine brain membranes, respectively.
When administered to mice at 16 mg/kg, intraperitoneally, JZL184 reduces
MAGL activity by 85%, elevates brain 2-AG levels by 8-fold, and elicits
analgesic activity in a variety of pain assays that qualitatively mimics
direct central cannabinoid (CB1) agonists. |
|
Ki16425 |
CAY-10012659 |
|
|
|
Lysophosphatidic acid
(LPA) is a bioactive lipid mediator that signals through five distinct G
protein-coupled receptors (LPA1-5). Ki16425 is a LPA receptor antagonist
with selectivity for LPA1 and LPA3. It exhibits Ki values of 0.34, 6.5,
and 0.93 M for the human LPA1, LPA2, and LPA3 receptors, respectively,
as determined by measuring inositol phosphate production in
RH7777-transfected cells. Ki1642, at 10 M, significantly blocks the
response of a variety of cancer cell lines to LPA-induced cell
migration. |
|
KRP 203 |
CAY-10010426 |
|
|
|
Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid metabolite
involved in many critical cellular processes including proliferation,
survival, and migration, as well as angiogenesis and immune responses.
Activation of sphingosine kinase by a variety of agonists increases
intracellular S1P, which in turn can function intracellularly as a
second messenger or be secreted out of the cell and act extracellularly
by signaling through S1P receptors (S1P1-5). KRP 203 is a selective S1P1
agonist that has been shown to reduce peripheral lymphocyte infiltration
and to prolong survival in rat transplant models. The phosphorylated
form of KRP 203 demonstrates a high affinity for the S1P1 with an ED50
value in the nM range and an ED50 value >1 M for S1P3. While the immune
modulating effects of KRP 203 are comparable to FTY720 (a non-selective
S1P agonist), the incidence of bradycardia is reduced 10-fold with KRP
203 compared to FTY720. |
|
KRP 203-phosphate |
CAY-10010427 |
|
|
|
Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid metabolite
involved in many critical cellular processes including proliferation,
survival, migration, as well as angiogenesis and immune responses. S1P
signals through five different S1P (S1P1-5) receptors. KRP 203 (Catalog
No. 10010426) is a selective S1P1 receptor agonist that acts as an
immunosuppressant., prolonging survival in rat transplant models. KRP
203 is rapidly phosphorylated in vivo, indicating that KRP 203 acts as a
prodrug for the actual S1P agonist, KRP 203-phosphate. Like KRP 203,
KRP203-phosphate is a selective S1P1 receptor agonist, demonstrating a
high affinity for S1P1 (ED50 value in the nM range) but not S1P3 (ED50
>1 M). Thus, the immunosuppressive effects of KRP 203 are comparable to
FTY720 (a non-selective S1P receptor agonist), while the incidence of
bradycardia is reduced 10-fold with KRP 203-phosphate compared to
FTY720. When combined with low dose cyclosporine A, KRP 203-phosphate
prolongs allograft survival and improves graft function. |
|
KT 5720 |
CAY-10011011 |
|
|
|
Protein kinase A
(PKA) regulates multiple signal transduction events via protein
phosphorylation and is integral to all cellular responses involving the
cyclic AMP second messenger system. KT 5720 is one of a family of
compounds synthesized by the fungus Nocardiopsis sp.. It blocks PKA
signaling through competitive inhibition of ATP with a Ki value of 60
nM. Reported IC50 values vary widely depending upon ATP concentration
tested and can range from 56 nM (low ATP) to 3 M (physiologic ATP).
Non-specific effects of KT 5720 include inhibition of phosphorylase
kinase, PDK1, MEK, MSK1, PKBα, and GSK 3β at concentrations as effective
as or more potent than that for inhibition of PKA. |
|
KT 5823 |
CAY-10010965 |
|
|
|
The activity of
cGMP-dependent protein kinase (PKG) is controlled by factors that
elevate cellular cGMP, like nitric oxide (NO), and by those that reduce
cGMP levels, like certain phosphodiesterases. KT 5823 is a potent,
selective inhibitor of PKG (in vitro IC50 value = 234 nM). KT 5823 is
cell-permeable and is often used in intact cells to assess the role of
PKG in signaling, although there are cases where it poorly inhibits PKG
in cells. KT 5823 is a weak inhibitor of PKC (Ki = 4 M) and PKA (Ki > 10
M). |
|
L-161,982 |
CAY-10011565 |
|
|
|
Prostaglandin E2
(PGE2) exerts its effects through four separate G coupled-protein
receptors (EP1-4). L-161,982 is a potent and selective EP4 receptor
antagonist. It demonstrates selective binding to human EP4 receptors
with a Ki value of 0.024 M compared to other receptors of the prostanoid
family, EP1, EP2, EP3, DP, FP, and IP, with Ki values of 17, 23, 1.9,
5.10, 5.63, and 6.74 M, respectively. L-161,982 at 10 mg/kg/day
suppresses PGE2-stimulated bone formation in young rats and at 100 nM
reverses the anti-inflammatory action of PGE2 in LPS-activated human
macrophages. At 10 M L-161982 blocks PGE2-induced cell proliferation in
HCA-7 colon cancer cells. |
|
Lacosamide |
CAY-10012592 |
|
|
|
Lacosamide, marketed
under the trade name Vimpat, is used for the adjunctive treatment of
partial-onset seizures and neuropathic pain. In a large double-blind,
randomized clinical trial of epileptic patients, lacosamide reduced
seizure frequency by 39% when administered twice daily at a dose of
400-600 mg in conjunction with other antiepiletics. In a small trial of
patients suffering from diabetic neuropathy, lacosamide significantly
attenuated pain compared to placebo. Lacosamide selectively enhances
sodium channel slow inactivation, without affecting fast inactivation as
with other antiepileptic drugs. The neuroprotective effects of
lacosamide are also attributed to its ability to modulate collapsin
response mediator protein-2, a member of the semaphorin signal
transduction pathway. |
|
Latrunculin B |
CAY-10010631 |
|
|
|
The latrunculins are
commonly used to experimentally disrupt the actin cytoskeleton of cells.
Latrunculin B causes concentration-dependent changes in cell shape and
actin organization. It sequesters G-actin and prevents F-actin assembly.
It binds monomeric actin with 1:1 stoichiometry and can be used
to block actin polymerization both in vitro and in cells (Kd = 60 nM).
The short-term effects of latrunculin B are comparable to those of
latrunculin A, although latrunculin B is slightly less potent. However,
latrunculin B is gradually inactivated by serum so that induced changes
are transient in the continued presence of the compound. For this
reason, latrunculin B may have fewer unwanted effects than latrunculin A
and may be preferred for short-term studies. |
|
LED209 |
CAY-16844 |
|
|
|
Bacterial pathogens
require the conserved membrane histidine sensor kinase (QseC) to detect
both host-derived adrenergic signals and the bacterial autoinducer-3
(AI-3), thus activating a signaling cascade that induces virulence gene
expression. LED209 is a potent QseC inhibitor that blocks both
norepinephrine- and epinephrine-triggered QseC-dependent virulence gene
expression at 5 pM in vitro. While LED209 inhibits virulence of
enterohemorrhagic E. coli, S. typhimurium, and F. tularensis, it does
not inhibit pathogen growth, a highly desirable feature of antimicrobial
agents to prevent drug resistance. |
|
Leptin (human) EIA Kit |
CAY-500010 |
|
|
|
Leptin, the product
of the ob (obese) gene, is produced mainly in the adipose tissue, and is
considered to play an important role in appetite control, fat
metabolism, and body weight regulation. The primary effect of leptin
appears to be mediated by leptin receptors expressed mainly in the
hypothalamus. In humans, leptin levels correlate with body mass index
(BMI) and percentage body fat, and are elevated even in obese
individuals. Leptin has a dual action; it decreases the appetite and
increases energy consumption. Leptin is secreted in circadian fashion
with nocturnal rise in both lean and obese patients. Mutations of the ob
gene resulting in leptin deficiency are the cause of obesity in the
ob/ob mice suggesting that endogeneous leptin can normalize their body
weight. In contrast, human obese subjects may have high level of leptin,
indicating a mechanism of leptin resistance. This Enzyme Immunometric
Assay (EIA) is based on a double-antibody sandwich technique. The wells
of the plate supplied with the kit are coated with a polyclonal antibody
specific of human leptin. This antibody will bind any Leptin introduced
in the wells (sample or standard). |
|
Leukotriene B4 Lipid
Maps MS Standard |
CAY-10007240 |
|
|
|
Leukotriene B4 (LTB4)
is a dihydroxy fatty acid derived from arachidonic acid through the 5-LO
pathway. It promotes a number of leukocyte functions including
aggregation, stimulation of ion fluxes, enhancement of lysosomal enzyme
release, superoxide anion production, chemotaxis, and chemokinesis. In
subnanomolar ranges (3.9 x 10^-10 M), LTB4 causes chemotaxis and
chemokinesis in human polymorphonuclear leukocytes. At higher
concentrations, (1.0 x 10^-7 M), LTB4 leads to neutrophil aggregation
and degranulation as well as superoxide anion production. |
|
Leukotriene
B4-3-aminopropylamide |
CAY-20114 |
|
|
|
The effects of
leukotriene B4 (LTB4) are mediated by two receptors, BLT1 and BLT2.
LTB4-3-aminopropylamide is an analog of LTB4 that exhibits potent and
selective binding to the BLT1 receptor, having Ki values of 5.1 and
1,227 nM at BLT1 and BLT2, respectively. |
|
Linoleoyl glycine |
CAY-9000326 |
|
|
|
Arachidonyl glycine,
the conjugate of arachidonic acid and glycine produced in mammalian
brain, skin, and spinal cord, is a structural analog of anandamide that
is reported to have analgesic activities in whole animal experiments. It
has poor affinity for the central cannabinoid (CB1) receptor,
high-affinity for the G protein-coupled receptor GPR-18, and is
metabolically regulated by fatty acid amide hydrolase (FAAH) activity.
LinGly is an endogenous homolog of linoleoyl ethanolamide, an
arachidonyl glycine. It inhibits the hydrolysis of anandamide in
FAAH-containing N18TG2 cell membranes with an IC50 value of ~25 M, which
is less potent than that of arachidonyl glycine (IC50 = 7 M). The
biological significance of LinGly has not yet been determined. |
|
Lipid Droplets
Fluorescence Assay Kit |
CAY-500001 |
|
|
|
Caymans Lipid
Droplets Fluorescence Assay Kit can be used to study regulators of lipid
droplet biogenesis in a variety of conditions, including inflammation.
The main advantage of this assay is that the green fluorescence of Nile
Red is both very sensitive and specific for lipid droplets. Furthermore,
changes in lipid droplet biogenesis in various cell types in response to
different manipulations can be both qualified and quantified by
fluorescence microscopy, flow cytometry, or fluorescence plate readers. |
|
|
|
Simultaneous
visualization of lipid droplets and associated proteins is also possible
when used with an antibody conjugated to a blue fluorophore. Oleic acid,
which is commonly used to induce lipid droplet formation in cultured
cells, is included as a positive control. |
|
|
|
This kit provides
sufficient reagent to effectively treat/stain 480 individual wells of
cells when utilized in a 96-well plate format. Lower density plates will
still require approximately the same amount of reagent on a per plate
basis. Therefore, in effect 5 plates worth of cells can be examined
irrespective of the number of wells/plate. Exceptions include protocols
in which non-adherent cells are utilized. |
|
Lipoxin A5 |
CAY-10011453 |
|
|
|
Lipoxin A5 (LXA5) is
produced by enzymatic transformation of EPA by leukocytes. LXA5 slowly
contracts pulmonary parenchymal strips from guinea pig with similar
potency to that of LXA4 and LXB4. However, LXA5 does not exert the
vasodilatory effects on aortic smooth muscle exhibited by LXA4 and LXB4. |
|
Lisinopril |
CAY-16833 |
|
|
|
Angiotensin-converting enzyme (ACE) removes the C-terminal dipeptide
from angiotensin I to form angiotensin II, a powerful vasoconstrictor.
ACE is a key regulator of the renin-angiotensin system and an important
drug target for the treatment of hypertension, congestive heart failure,
and heart attacks, and also in preventing renal and retinal
complications in diabetes. Lisinopril is a potent ACE inhibitor that
inhibits the formation of angiotensin I with an IC50 value of 1.2 nM
(ovine) and displays ID50 values of 2.3 and 6.5 g/kg in rat and canine,
respectively. At 0.1 nM lisinopril reduces the formation of endothelin-1
and increases nitric oxide in human vascular endothelial cells. |
|
Liver X Receptor
Transcription Factor Assay Kit |
CAY-10011119 |
|
|
|
Liver X receptors
(LXRs) are ligand-activated transcription factors that are primarily
activated by oxysterols and cholesterol metabolites. As such, LXRs play
an important role in the regulation of cholesterol, lipid, and
carbohydrate metabolism. There are two known isoforms of LXR: LXRa and
LXR. LXR is ubiquitously expressed in all tissues while LXRa is
primarily expressed in the liver, adipose tissue, small intestine, and
macrophages. LXRs are currently being examined as potential therapeutic
targets in the treatment of diabetes, cardiovascular disease, Alzheimers
disease, obesity, and atherosclerosis. Cayman's LXR Transcription Factor
Assay Kit is a sensitive colorimetric method for detecting specific
transcription factor binding activity from nuclear exctracts and whole
cell lysates in a 96-well format. |
|
L-N5-(1-Imino-3-pentenyl) Ornithine (hydrochloride) |
CAY-10011724 |
|
|
|
ENIPO is a potent,
selective inhibitor of iNOS. The Ki values for inhibition of iNOS, nNOS,
and eNOS by ENIPO are 17, 10.3 and 58.2 M, respectively, as determined
using initial rate binding kinetics. However, ENIPO is a time-dependent
inhibitor that, with longer incubations, demonstrates reversible tight
binding inhibition that is selective for iNOS over nNOS or eNOS. This
selectivity results from iNOS exhibiting a 4-fold faster binding and
10-fold slower dissociation with ENIPO compared to nNOS. Ki values for
ENIPO binding to iNOS and nNOS are 0.56 and 6 M, respectively. Accurate
determination of the Ki value of ENIPO for eNOS has not been determined
but is expected to be 50-fold less than iNOS. |
|
L-Ornithine 13C
(hydrochloride) |
CAY-10010661 |
|
|
|
Ornithine is an amino
acid produced in the urea cycle by the splitting off of urea from
arginine. |
|
LSD1 (human
recombinant) |
CAY-10245 |
|
|
|
Source: human
recombinant N-terminal hexahistidine tagged enzyme expressed in E. coli;
BC048134 Mr: 94 kDa |
|
LSD1 Inhibitor
Screening Assay Kit |
CAY-700120 |
|
|
|
Lysine-specific
demethylase 1 (LSD1) is a histone demethylase whose actions on specific
lysine residues repress transcription of chromosomal DNA. LSD1 also
inhibits the tumor suppressor activity of p53 by demethylating a
specific lysine residue. Inhibitors of LSD1 are important tools used to
elucidate mechanisms of transcription and cell cycle progression and
have therapeutic potential for treating cancer. Cayman's LSD1 Inhibitor
Screening Assay Kit provides a convenient fluorescence-based method for
screening LSD1-specific inhibitors. The assay is based on the multistep
enzymatic reaction in which LSD1 first produces H2O2 during the
demethylation of lysine 4 on a peptide corresponding to the first 21
amino acids of the N-terminal tail of histone H3. In the presence of
horseradish peroxidase, H2O2 reacts with ADHP to produce the highly
fluorescent compound resorufin that can be analyzed with an excitation
wavelength of 530-540 nm and an emission wavelength of 585-595 nm. |
|
Lubiprostone |
CAY-10010487 |
|
|
|
Lubiprostone is a
bicyclic prostaglandin E1 (PGE1) derivative that specifically activates
ClC-2 chloride channels in gastrointestinal epithelial cells, promoting
the efflux of chloride and water. Lubiprostone, sold under the trade
name Amitiza, effectively treats idiopathic chronic constipation in
adults when given at a dose of 24 μg twice daily. It is also used to
treat irritable bowel syndrome with constipation. Unlike many other
treatments for constipation, lubiprostone does not show signs of
tolerance, dependency, or rebound. Lubiprostone may also accelerate
recovery of mucosal barrier function in damaged intestine , mimicking
the gastroprotective effects of PGE2. |
|
Luminex Leukotriene B4 Kit |
CAY-500260 |
|
|
|
Leukotriene B4 (LTB4)
is a potent mediator of inflammation that stimulates a number of
leukocyte functions, including aggregation, stimulation of ion fluxes,
enhancement of lysosomal enzyme release, superoxide anion production,
chemotaxis, and chemokinesis. In subnanomolar ranges (3.9 x 10-10 M),
LTB4 causes chemotaxis and chemokinesis in human PMNLs. At higher
concentrations, (1.0 x 10-7 M), LTB4 leads to neutrophil aggregation and
degranulation as well as superoxide anion production. Plasma levels of
LTB4 increase from <100 pg/ml to >100 ng/ml following leukocyte
stimulation. Caymans Luminex LTB4 Kit can be used for quantification of
LTB4 in plasma, culture media, and other sample matrices. This kit
typically displays an IC50 (50% B/B0) of approximately 140 pg/ml and a
detection limit (80% B/B0) of approximately 25 pg/ml. |
|
LY223982 |
CAY-10010024 |
|
|
|
Leukotriene B4 (LTB4)
is a dihydroxy fatty acid derived from the 5-lipoxygenase (5-LO) pathway
of arachidonic acid metabolism and is an important mediator of the
inflammatory process. The benzophenone dicarboxylic acid derivative
LY223982 is a potent BLT1 receptor antagonist. It inhibits the specific
binding of radiolabeled-LTB4 to isolated human neutrophils with an IC50
value of 13.2 nM. LY223982 inhibits the LTB4-induced aggregation of
guinea pig and human neutrophils with IC50 values of 74 and 100 nM,
respectively. However, concentrations of LY223982 up tp 10 M do not
inhibit binding of LTB4 to human BLT1 or BLT2 expressed in CHO cells. |
|
LY293111 |
CAY-10009768 |
|
|
|
Leukotriene B4 (LTB4)
is a dihydroxy fatty acid derived from the 5-lipoxygenase pathway of
arachidonic acid metabolism and is an important mediator of the
inflammatory process. LY293111 is a potent antagonist of the LTB4
receptor, BLT1, that inhibits the specific binding of radiolabeled-LTB4
to isolated human neutrophils with an IC50 value of 17.6 nM and inhibits
the LTB4-induced chemotaxis of human neutrophils with an IC50 value of
6.3 nM. LY293111 inhibits growth of MiaPaCa-2 and AsPC-1 human
pancreatic cancer cells in vitro (250-1,000 nM) and subcutaneous
xenografts in athymic mice (250 mg/kg/day), inducing apoptosis and
S-phase arrest. |
|
Methylcarbamyl PAF C-8 |
CAY-9000332 |
|
|
|
Methylcarbamyl PAF
C-8 is the C-8 analog of Methylcarbamyl PAF C-16. Methylcarbamyl PAF
C-16 is a stable analog of PAF C-16 with a half-life greater than 100
minutes in platelet poor plasma due to its resistance to degradation by
PAF-AH. It is nearly equipotent with PAF C-16 in its ability to induce
platelet aggregation both in isolated platelets and in platelet-rich
plasma. In NRK-49 cells overexpressing the PAF receptor, both PAF C-16
and methylcarbamyl PAF C-16 cause the induction of c-myc, c-fos, and the
activation of mitogen-activated protein kinase. Methylcarbamyl PAF C-16
induces G1 phase cell cycle arrest, suggesting a potential role for PAF
in the inhibition of oncogenic transformation. |
|
Methyltransferase
Colorimetric Assay Kit |
CAY-700140 |
|
|
|
Methylation of key
biological molecules and proteins plays important roles in numerous
biological systems, including signal transduction, biosynthesis, protein
repair, gene silencing, and chromatin regulation. The
S-adenosylmethionine (SAM) dependent methyltransferases use SAM, the
second most commonly used enzymatic cofactor after ATP. SAM, also known
as AdoMet, acts as a donor of a methyl group that is required for the
modification of proteins and DNA. Aberrant levels of SAM have been
linked to many abnormalities, including Alzheimers Disease, depression,
Parkinsons Disease, multiple sclerosis, liver failure, and cancer.
Caymans Methyltransferase Colorimetric Assay Kit is a continuous
enzyme-coupled assay that can continuously monitor SAM-dependent
methyltransferases. The removal of the methyl group from SAM generates
S-adenosylhomocysteine (AdoHcy), which is rapidly converted to
S-ribosylhomocysteine and adenine by AdoHcy nucleosidase. This rapid
conversion prevents the buildup of AdoHcy and its feedback inhibition on
the methylation reaction. Finally, the adenine is converted to
hypoxanthine, by adenine deaminase, which in turn is converted to urate
and hydrogen peroxide (H2O2). The rate of production of H2O2 is measured
with the colorimetric reagent, 3,5-dichloro-2-hydroxybenzenesulfonic
acid, by an increase in absorbance at 500-520 nm. The assay is supplied
with AdoHcy as a positive control. The assay can be used with any
purified SAM-dependent methyltransferase. |
|
Methyltransferase
Fluorometric Assay Kit |
CAY-700150 |
|
|
|
Methylation of key
biological molecules and proteins play important roles in numerous
biological systems, including signal transduction, biosynthesis, protein
repair, gene silencing, and chromatin regulation. The
S-adenosylmethionine (SAM) dependent methyltransferases use SAM, the
second most commonly used enzymatic cofactor after ATP. SAM, also known
as AdoMet, acts as a donor of a methyl group that is required for the
modification of proteins and DNA. Aberrant levels of SAM have been
linked to many abnormalities, including Alzheimers Disease, depression,
Parkinsons Disease, multiple sclerosis, liver failure, and cancer.
Cayman's Methyltransferase Fluorometric Assay Kit is a continuous
enzyme-coupled assay that can continuously monitor SAM-dependent
methyltransferases. The removal of the methyl group from SAM generates
S-adenosylhomocysteine (AdoHcy), which is rapidly converted to
S-ribosylhomocysteine and adenine by AdoHcy nucleosidase. This rapid
conversion prevents the buildup of AdoHcy and its feedback inhibition on
the methylation reaction. Finally, the adenine is converted to
hypoxanthine, by adenine deaminase, which in turn is converted to urate
and hydrogen peroxide (H2O2). The reaction between H2O2 and ADHP
(10-acetyl-3,7,-dihydroxyphenoxazine) produces the highly fluorescent
compound resorufin. Resorufin fluorescence can be easily analyzed with
an excitation wavelength of 530-540 nm and an emission wavelength of
585-595 nm. The assay is supplied with AdoHcy as a positive control. The
assay can be used with any purified SAM-dependent methyltransferase. |
|
MG132 |
CAY-10012628 |
|
|
|
The
ubiquitin-proteasome pathway plays an integral role in the selective
degradation of intracellular proteins. While important for clearing
damaged or misfolded proteins, this proteolytic pathway also regulates
the availability of key proteins involved in the control of inflammatory
processes, cell cycle regulation, and gene expression. MG132 is a
potent, reversible and cell permeable proteasome inhibitor that inhibits
cell growth in B16 and IPC227F cells with IC50 values of 42 and 77 nM,
respectively. MG132 at 10 M inhibits NF-κB activation, sensitizing a
variety of carcinoma cell lines to apoptosis. |
|
MRE-269 |
CAY-10010412 |
|
|
|
Prostacyclin (PGI2)
is a potent vasorelaxant and inhibitor of platelet aggregation. It
mediates its actions by binding to a specific G protein-coupled
receptor, the IP receptor, on the surface of endothelial cells, arterial
smooth muscle, and platelets. The IP receptor also participates in
signal transduction of the pain response, cardioprotection, and
inflammation. MRE-269 is the active form of the prodrug NS-304. It is a
potent and selective agonist for the human IP receptor with a Ki value
of 20 nM. In contrast to PGI2, which has a half-life of 30 seconds to a
few minutes in vivo, plasma concentrations of MRE-269 remain near peak
levels for more than eight hours in rats and dogs. Unlike the PGI2
analogues, beraprost and iloprost, MRE-269 lacks high affinity for the
EP3 receptor. As a result, MRE-269 induces vasodilation equally in large
and small pulmonary arteries, whereas vasodilation of small arteries by
beraprost and iloprost is reduced via EP3-mediated vasoconstriction. |
|
Myeloperoxidase
Chlorination Assay Kit |
CAY-10006438 |
|
|
|
Myeloperoxidase (MPO)
is a member of the heme peroxidase superfamily and is stored within the
azurophilic granules of leukocytes. MPO is found within circulating
neutrophils, monocytes, and some tissue macrophages. A unique activity
of MPO is its ability to use chloride as a cosubstrate with hydrogen
peroxide (H2O2) to generate chlorinating oxidants such as hypochlorous
acid, a potent antimicrobial agent. Recently, evidence has emerged that
MPO-derived oxidants contribute to tissue damage and the initiation and
propagation of acute and chronic vascular inflammatory diseases. The
fact that circulating levels of MPO have been shown to predict risks for
major adverse cardiac events and that levels of MPO-derived chlorinated
compounds are specific biomarkers for disease progression, has attracted
considerable interest in the development of therapeutically useful MPO
inhibitors. MPO also oxidizes a variety of substrates, including phenols
and anilines, via the classic peroxidation cycle. The relative
concentrations of chloride and the reducing substrate determine whether
MPO uses H2O2 for chlorination or peroxidation. Assays based on
measurement of chlorination activity are more specific for MPO than
those based on peroxidase substrates because peroxidases generally do
not produce hypochlorous acid. The only exception is eosinophil
peroxidase that produces hypochlorous acid at pH below 5. The
chlorination activity of MPO has a neutral pH optimum, therefore the
assay conditions can be set so that only MPO activity is specifically
measured. Caymans Myeloperoxidase Chlorination Assay provides a
convenient fluorescence-based method for detecting the MPO chlorination
activity in both crude cell lysates and purified enzyme preparations.
The assay utilizes the non-fluorescent
2-[6-(4-aminophenoxy)-3-oxo-3H-xanthen-9-yl]-benzoic acid (APF), which
is selectively cleaved by hypochlorite (-OCl) to yield the highly
fluorescent compound fluorescein. Fluorescein fluorescence is analyzed
with an excitation wavelength of 480-490 nm and an emission wavelength
of 515-520 nm. The kit includes a MPO-specific inhibitor for
distinguishing MPO activity from non-MPO-independent fluorescence. |
|
Myeloperoxidase
Inhibitor Screening Assay Kit |
CAY-700170 |
|
|
|
Myeloperoxidase (MPO)
is a member of the heme peroxidase superfamily and is stored within the
azurophilic granules of leukocytes. MPO is found within circulating
neutrophils, monocytes, and some tissue macrophages. A unique activity
of MPO is its ability to use chloride as a cosubstrate with hydrogen
peroxide to generate chlorinating oxidants such as hypochlorous acid, a
potent antimicrobial agent. Recently, evidence has emerged that
MPO-derived oxidants contribute to tissue damage and the initiation and
propagation of acute and chronic vascular inflammatory diseases. The
fact that circulating levels of MPO have been shown to predict risks for
major adverse cardiac events and that levels of MPO-derived chlorinated
compounds are specific biomarkers for disease progression, has attracted
considerable interest in the development of therapeutically useful MPO
inhibitors. MPO also oxidizes a variety of substrates, including phenols
and anilines, via the classic peroxidation cycle. The relative
concentrations of chloride and the reducing substrate determine whether
MPO uses hydrogen peroxide for chlorination or peroxidation. Assays
based on measurement of chlorination activity are more specific for MPO
than those based on peroxidase substrates because peroxidases generally
do not produce hypochlorous acid. However, it is important that when
screening for MPO inhibition that both the chlorination and peroxidation
activities be tested. This determines whether the inhibitor specifically
interferes with the chlorination and/or peroxidation cycle or whether
the inhibitor simply acts as a scavenger for hypochlorous acid. Also,
many reversible inhibitors act by diverting MPO from the chlorinating
cycle to the peroxidase cycle. Caymans MPO Inhibitor Screening Assay
provides convenient fluorescence-based methods for screening inhibitors
to both the chlorination and peroxidation activities of MPO. The
chlorination assay utilizes the non-fluorescent
2-[6-(4-aminophenoxy)-3-oxo-3H-xanthen-9-yl]-benzoic acid (APF), which
is selectively cleaved by hypochlorite (-OCl) to yield the highly
fluorescent compound fluorescein. Fluorescein fluorescence is analyzed
with an excitation wavelength of 480-490 nm and an emission wavelength
of 515-520 nm. The peroxidation assay utilizes the peroxidase component
of MPO. The reaction between hydrogen peroxide and ADHP
(10-acetyl-3,7-dihydroxyphenoxazine) produces the highly fluorescent
compound resorufin. Resorufin fluorescence is analyzed with an
excitation wavelength of 530-540 nm and an emission wavelength of
585-595 nm. |
|
Myeloperoxidase
Peroxidation Assay Kit |
CAY-700160 |
|
|
|
Myeloperoxidase (MPO)
is a member of the heme peroxidase superfamily and is stored within the
azurophilic granules of leukocytes. MPO is found within circulating
neutrophils, monocytes, and some tissue macrophages. A unique activity
of MPO is its ability to use chloride as a cosubstrate with hydrogen
peroxide to generate chlorinating oxidants such as hypochlorous acid, a
potent antimicrobial agent. Recently, evidence has emerged that
MPO-derived oxidants contribute to tissue damage and the initiation and
propagation of acute and chronic vascular inflammatory diseases. The
fact that circulating levels of MPO have been shown to predict risks for
major adverse cardiac events and that levels of MPO-derived chlorinated
compounds are specific biomarkers for disease progression, has attracted
considerable interest in the development of therapeutically useful MPO
inhibitors. MPO also oxidizes a variety of substrates, including phenols
and anilines, via the classic peroxidation cycle. The relative
concentrations of chloride and the reducing substrate determine whether
MPO uses hydrogen peroxide for chlorination or peroxidation. Caymans MPO
Peroxidation Assay provides a convenient fluorescence-based method for
detecting the MPO peroxidase activity in both crude cell lysates and
purified enzyme preparations. The assay utilizes the peroxidase
component of MPO. The reaction between hydrogen peroxide and ADHP
(10-acetyl-3,7-dihydroxyphenoxazine) produces the highly fluorescent
compound resorufin. Resorufin fluorescence can be easily analyzed with
an excitation wavelength of 530-540 nm and emission wavelength of
585-595 nm. The kit includes a MPO-specific inhibitor for distinguishing
between MPO activity from non-MPO-independent fluorescence. |
|
Myricetin |
CAY-10012600 |
|
|
|
Myricetin is a
flavonoid compound found in many fruits and vegetables, including red
wine, that acts as a powerful antioxidant. Myricetin inhibits TBARS
formation with an IC50 value of 6.34 and at 20 M, blocks oxLDL uptake by
U937-derived macrophages, reducing CD36 expression. Myricetin
demonstrates potent chemopreventative potential by binding JAK1/STAT3 to
inhibit the neoplastic transformation of murine JB6 P+ cells and
inhibiting MEK1 kinase activity. |
|
N-(-ketocaproyl)-L-Homoserine lactone |
CAY-10011207 |
|
|
|
AHLs vary in acyl
group length (C4-C18), in the substitution of C3 (hydrogen, hydroxyl, or
oxo group), and in the presence or absence of one or more carbon-carbon
double bonds in the fatty acid chain.
These differences confer signal specificity through the affinity
of transcriptional regulators of the LuxR family. |
|
|
|
In one of the
most-studied quorum-sensing systems in gram-negative bacteria, the LuxI
AHL synthase catalyzes the production of 3-O-C6-(L)-HSL utilizing
S-adenosylmethionine and hexanoyl-acyl carrier protein as reaction
substrates in the marine bioluminescence bacterium V.fischeri. At
increased populations of the bacteria, localized higher concentrations
of 3-O-C6-HSL, an endogenous ligand to transcriptional factor LuxR, lead
to increased production of both the AHL synthase and proteins
responsible for bioluminescence. Numerous other species of bacteria also
employ 3-O-C6-HSL in cell-to-cell communication. |
|
N-3-oxo-hexadec-11Z-enoyl-L-Homoserine lactone |
CAY-10011238 |
|
|
|
Quorum sensing is a
regulatory system used by bacteria for controlling gene expression in
response to increasing cell density. This regulatory process manifests
itself with a variety of phenotypes including biofilm formation and
virulence factor production. Coordinated gene expression is achieved by
the production, release, and detection of small diffusible signal
molecules called autoinducers. The N-acylated homoserine lactones (AHLs)
comprise one such class of autoinducers, each of which generally
consists of a fatty acid coupled with homoserine lactone (HSL).
Regulation of bacterial quorum sensing signaling systems to inhibit
pathogenesis represents a new approach to antimicrobial therapy in the
treatment of infectious diseases. AHLs vary in acyl group length
(C4-C18), in the substitution of C3 (hydrogen, hydroxyl, or oxo group),
and in the presence or absence of one or more carbon-carbon double bonds
in the fatty acid chain. These differences confer signal specificity
through the affinity of transcriptional regulators of the LuxR family.
3-O-C16:1-Δ11cis-(L)-HSL is a single, positional (carbon-carbon double
bond between C11 and C12 of the N-3-oxo-acyl side chain), geometric
(cis, or Z geometry), and stereoisomer (L, or S absolute stereochemistry
at the 3-position of the homoserine lactone ring) of what is generally
referred to as 3-O-C16:1-HSL. An unspecified positional and geometric
isomer of 3-O-C16:1-(L)-HSL is produced by the F2/5 strain of
Agrobacterium vitis, the bacterium responsible for grape crown gall and
its resulting loss of agricultural productivity. |
|
N-acetyl-D-Glucosamine |
CAY-13136 |
|
|
|
N-acetyl-D-Glucosamine (GlcNAc) is a monosaccharide derivative of
glucose. It is released by the action of O-GlcNAcase, in mammalian
systems from proteins that have been post-translationally modified with
O-GlcNAc. Levels of O-GlcNAcylation proteins from Alzheimers disease
brain extracts are decreased as compared to that in controls, suggesting
that release of GlcNAc may contribute to pathogenesis. In E. coli,
GlcNAc induces the expression of multidrug exporter genes, indicating
that this sugar can alter gene expression. GlcNAc is also the monomeric
unit of chitin, which is found in fungi and many invertebrates,
including crustaceans, insects, and nematodes. For this reason,
chemicals that inhibit the incorporation of GlcNAc into chitin are
cytotoxic to these organisms. |
|
N-acetyl-D-Mannosamine |
CAY-10011060 |
|
|
|
Sialic acids,
commonly present as terminal carbohydrates on glycoconjugates, are
essential for a variety of cellular functions including cell adhesion
and signal recognition as well as the formation and progression of
tumors. Disruption of sialic acid biosynthesis can result in severe
glomerular proteinuria or neuromuscular disorders such as hereditary
inclusion body myopathy (HIBM). N-Acetyl-D-mannosamine (ManNAc) is the
precursor of all physiological sialic acids. Intraperitoneal injection
of ManNAc twice daily at 1,000 mg/kg in C57BL/6 mice for 13 days leads
to increased sialylation in kidney, liver, blood cells, brain, spinal
cord, muscle, heart, lung, and spleen. ManNAc reverses hyposialylation
and improves glomerular integrity in GneM712T/M712T mice whose key
enzyme for sialic acid production has been deleted and may prove
therapeutic in the treatment of HIBM. |
|
NAPE-PLD (159-172)
Polyclonal Antibody |
CAY-10305 |
|
|
|
N-acylethanolamines
(NAEs) are involved in diverse biological processes such as inflammatory
regulation, apoptosis, and tissue degeneration. In animals, NAEs are
mainly biosynthesized via a membrane phospholipid-dependent pathway,
which is the enzymatic hydrolysis of N-acyl-phosphatidylethanolamine
(NAPE). The enzyme catalyzing this reaction is a phospholipase D subtype
selective for NAPE named N-acyl-phosphatidylethanolamine-hydrolysing
phospholipase D (NAPE-PLD). It has been cloned from mouse, rat, and
human and is 393-396 amino acids in length, with an estimated molecular
weight of 46 kDa. Both NAPE-PLD mRNA and protein activity have been
detected in a wide range of tissues with the highest levels in brain,
kidney, and testis. In rat, NAPE-PLD activity in the brain is low in
neonates and is 15-fold higher in adults, whereas the activity remains
constant in the heart during development. CAY-10305 |
|
NAPE-PLD (6-20)
Polyclonal Antibody |
CAY-10306 |
|
|
|
N-acylethanolamines
(NAEs) are involved in diverse biological processes such as inflammatory
regulation, apoptosis, and tissue degeneration. In animals, NAEs are
mainly biosynthesized via a membrane phospholipid-dependent pathway,
which is the enzymatic hydrolysis of N-acyl-phosphatidylethanolamine
(NAPE). The enzyme catalyzing this reaction is a phospholipase D subtype
selective for NAPE named N-acyl-phosphatidylethanolamine-hydrolysing
phospholipase D (NAPE-PLD). It has been cloned from mouse, rat, and
human and is 393-396 amino acids in length, with an estimated molecular
weight of 46 kDa. Both NAPE-PLD mRNA and protein activity have been
detected in a wide range of tissues with the highest levels in brain,
kidney, and testis. In rat, NAPE-PLD activity in the brain is low in
neonates and is 15-fold higher in adults, whereas the activity remains
constant in the heart during development. |
|
Naphthofluorescein |
CAY-13055 |
|
|
|
Furin is a proprotein
convertase, converting precursor proteins to functional proteins within
the Golgi/trans-Golgi secretory pathway. Naphthofluorescein is a
cell-permeable inhibitor of furin (IC50 = 12 μM). It inhibits
furin-mediated cleavage of the pro-form of membrane type-1 matrix
metalloproteinase MT1-MMP, resulting in decreased levels of active
MT1-MMP. This, in turn, suppresses MMP-2 activation and reduces cell
motility in CHO cells expressing proMT1-MMP. Napthofluorescein
significantly inhibits the invasion of Matrigel by the human
fibrosarcoma cell line, HT1080. The effects of this furin inhibitor on
other furin-mediated processes, in vivo or in vitro, remain to be
determined. |
|
NBD-Stearoyl-2-Arachidonoyl-sn-glycerol |
CAY-10011300 |
|
|
|
1-Stearoyl-2-arachidonoyl-sn-glycerol is a diacylglycerol (DAG) that
contains stearic acid in the sn-1 site and arachidonic acid at the sn-2
position of the glycerol backbone, as is commonly found in DAG from
biological phospholipids. NBD-Stearoyl-2-arachidonoyl-sn-glycerol has
the fluorophore nitrobenzoxadiazole (NBD) attached to the ω-end of the
stearoyl chain of 1-stearoyl-2-arachidonoyl-sn-glycerol. Fluorescently
tagged lipids have been used to study their interactions with proteins,
their utilization by cells and liposomes, and for the development of
assays for lipid metabolism. |
|
N-butyryl-L-Homocysteine thiolactone |
CAY-10011204 |
|
|
|
Quorum sensing is a
regulatory system used by bacteria for controlling gene expression in
response to increasing cell density. Controlling bacterial infections by
quenching their quorum sensing systems is a promising field of study.
The expression of specific target genes, such as transcriptional
regulators belonging to the LuxIR family of proteins, is coordinated by
synthesis of diffusible acylhomoserine lactone (AHL) molecules.
N-butyryl-L-Homocysteine thio-lactone is an analog of
N-butyryl-L-homoserine lactone, the small diffusible signaling molecule
involved in quorum sensing, thereby controlling gene expression and
cellular metabolism. N-butyryl-L-Homocysteine thio-lactone induces
violacein expression in C. violaceum mutants usually not able to produce
AHLs. |
|
N-cis-hexadec-9-enoyl-L-Homoserine lactone |
CAY-10012673 |
|
|
|
Quorum sensing is a
regulatory process used by bacteria for controlling gene expression in
response to increasing cell density. This regulatory process manifests
itself with a variety of phenotypes including biofilm formation and
virulence factor production. Coordinated gene expression is achieved by
the production, release, and detection of small diffusible signal
molecules called autoinducers. The N-acylated homoserine lactones (AHLs)
comprise one such class of autoinducers, each of which generally
consists of a fatty acid coupled with homoserine lactone (HSL). AHLs
vary in acyl group length (C4-C18), in the substitution of C3 (hydrogen,
hydroxyl, or oxo group) and in the presence or absence of one or more
carbon-carbon double bonds in the fatty acid chain. These differences
confer signal specificity through the affinity of transcriptional
regulators of the LuxR family. C16-HSL is a long-chain AHL that
functions as a quorum sensing signaling molecule in strains of S.
meliloti. Regulating bacterial quorum sensing signaling can be used to
inhibit pathogenesis and thus, represents a new approach to
antimicrobial therapy in the treatment of infectious diseases. |
|
N-cis-octadec-9-enoyl-L-Homoserine lactone |
CAY-10012674 |
|
|
|
Quorum sensing is a
regulatory process used by bacteria for controlling gene expression in
response to increasing cell density. This regulatory process manifests
itself with a variety of phenotypes including biofilm formation and
virulence factor production. Coordinated gene expression is achieved by
the production, release, and detection of small diffusible signal
molecules called autoinducers. The N-acylated homoserine lactones (AHLs)
comprise one such class of autoinducers, each of which generally
consists of a fatty acid coupled with homoserine lactone (HSL). AHLs
vary in acyl group length (C4-C18), in the substitution of C3 (hydrogen,
hydroxyl, or oxo group) and in the presence or absence of one or more
carbon-carbon double bonds in the fatty acid chain. These differences
confer signal specificity through the affinity of transcriptional
regulators of the LuxR family. C18-HSL is a long-chain AHL that may have
antimicrobial activity and thus, might be used to inhibit pathogenesis
by regulating bacerial quorum sensing signaling. |
|
N-cis-tetradec-9-enoyl-L-Homoserine lactone |
CAY-10012672 |
|
|
|
Quorum sensing is a
regulatory process used by bacteria for controlling gene expression in
response to increasing cell density. This regulatory process manifests
itself with a variety of phenotypes including biofilm formation and
virulence factor production. Coordinated gene expression is achieved by
the production, release, and detection of small diffusible signal
molecules called autoinducers. The N-acylated homoserine lactones (AHLs)
comprise one such class of autoinducers, each of which generally
consists of a fatty acid coupled with homoserine lactone (HSL). AHLs
vary in acyl group length (C4-C18), in the substitution of C3 (hydrogen,
hydroxyl, or oxo group) and in the presence or absence of one or more
carbon-carbon double bonds in the fatty acid chain. These differences
confer signal specificity through the affinity of transcriptional
regulators of the LuxR family. C14-HSL is a long-chain AHL that
functions as a signaling molecule in the quorum sensing of A. vitis.
Regulating bacterial quorum sensing signaling can be used to inhibit
pathogenesis and thus, represents a new approach to antimicrobial therpy
in the treatment of infectious diseases. |
|
N-Decanoyl-L-Homoserine lactone |
CAY-10011201 |
|
|
|
Quorum sensing is a
regulatory system used by bacteria for controlling gene expression in
response to increasing cell density. A promising field of study involves
controlling bacterial infections by quenching their quorum sensing
systems. The expression of specific target genes, such as
transcriptional regulators belonging to the LuxIR family of proteins, is
coordinated by synthesis of diffusible acylhomoserine lactone (AHL)
molecules. N-decanoyl-L-Homoserine lactone is a small diffusible
signaling molecule involved in quorum sensing, thereby controlling gene
expression and affecting cellular metabolism. The applications of this
molecule include regulation of virulence and exoproteases. |
|
N-dodecanoyl-L-Homoserine lactone |
CAY-10011203 |
|
|
|
Quorum sensing is a
regulatory system used by bacteria for controlling gene expression in
response to increasing cell density. Controlling bacterial infections by
quenching their quorum sensing systems is a promising field of study.
The expression of specific target genes, such as transcriptional
regulators belonging to the LuxR family of proteins, is coordinated by
the synthesis of diffusible acylhomoserine lactone (AHL) molecules.
N-dodecanoyl-L-Homoserine lactone (C12-HSL) is a small diffusible
signaling molecule involved in quorum sensing, thereby controlling gene
expression and affecting cellular metabolism in bacteria. In addition to
regulating bacterial functions, C12-HSL activates NF-κB in RAW 264.7
macrophages, increasing the expression of TNF-α, interleukin-1β (IL-1β),
and IL-8, while other lactones do not. In addition, C12-HSL alters cell
cycling and metabolism of human keratinocyte (HaCaT) cells. It is
important to note that C12-HSL is distinct from N-3-oxo-do
decanoyl-L-Homoserine lactone (Catalog No. 10007895), which is
produced at different times in biofilm development and has different
cellular effects. |
|
Neurodazine |
CAY-13224 |
|
|
|
Neurodazine induces
neuronal differentiation in skeletal muscle cells. In murine C2C12
myoblasts, neurodazine (2 μM for seven days) upregulated the expression
of neuron-specific enolase (NSE), neurofilament 200 (NF200), synapsin,
and other neuronal markers.
Neurodazine similarly upregulated NSE and NF200 in human skeletal muscle
fibers, indicating efficacy in mature muscle as well as in myoblasts |
|
NH125 |
CAY-10011250 |
|
|
|
NH125 is an imidazole
that has potent antibacterial properties in drug-resistant bacteria . In
bacteria, NH125 inhibits several histidine kinases, inhibiting YycG with
an IC50 of 6.6 M . NH125 also decreases the viability of several cancer
cell lines with IC50 values ranging from 0.7-4.7 M . In mammalian cells,
NH125 strongly inhibits eEF-2K (IC50 = 60 nM), with weaker effects on
protein kinase C (IC50 = 7.5 M), protein kinase A (IC50 = 80 M), and
calmodulin-dependent kinase II (IC50 = 100 M). |
|
N-heptanoyl-L-Homoserine lactone |
CAY-10011198 |
|
|
|
Quorum sensing is a
regulatory system used by bacteria for controlling gene expression in
response to increasing cell density. Controlling bacterial infections by
quenching their quorum sensing systems is involved in a promising field
of study. The expression of specific target genes, such as
transcriptional regulators belonging to the LuxIR family of proteins, is
coordinated by synthesis of diffusible acylhomoserine lactone (AHL)
molecules. N-heptanoyl-L-Homoserine lactone (C7-HSL) is a small
diffusible signaling molecule involved in quorum sensing, thereby
controlling gene expression and affecting cellular metabolism. The
diverse applications of this molecule include regulation of virulence,
infection prevention, and septicemia in fish. |
|
N-hexadecanoyl-L-Homoserine lactone |
CAY-13064 |
|
|
|
Quorum sensing is a
regulatory system used by bacteria for controlling gene expression in
response to increasing cell density. This regulatory process manifests
itself with a variety of phenotypes including biofilm formation and
virulence factor production. Coordinated gene expression is achieved by
the production, release, and detection of small diffusible signal
molecules called autoinducers. The N-acylated homoserine lactones (AHLs)
comprise one such class of autoinducers, each of which generally
consists of a fatty acid coupled with homoserine lactone (HSL).
Regulation of bacterial quorum sensing signaling systems to inhibit
pathogenesis represents a new approach to antimicrobial therapy in the
treatment of infectious diseases. AHLs vary in acyl group length
(C4-C18), in the substitution of C3 (hydrogen, hydroxyl, or oxo group),
and in the presence or absence of one or more carbon-carbon double bonds
in the fatty acid chain. These differences confer signal specificity
through the affinity of transcriptional regulators of the LuxR family.
C16-HSL is one of a number of lipophilic, long acyl side-chain bearing
AHLs, including its monounsaturated analog C16:1-(L)-HSL, produced by
the LuxI AHL synthase homolog SinI involved in quorum-sensing signaling
in Sinorhizobium meliloti, a nitrogen-fixing bacterial symbiont of
certain legumes. C16-HSL is the most abundant AHL produced by the
proteobacterium Rhodobacter capsulatus and activates genetic exchange
between R. capsulatus cells. N-Hexadecanoyl-L-homoserine lactone and
other hydrophobic AHLs tend to localize in relatively lipophilic
cellular environments of bacteria and cannot diffuse freely through the
cell membrane. The long-chain N-acylhomoserine lactones may be exported
from cells by efflux pumps or may be transported between communicating
cells by way of extracellular outer membrane vesicles. |
|
N-methyl Leukotriene C4 |
CAY-13390 |
|
|
|
Produced by
neutrophils, macrophages, and mast cells, and by transcellular
metabolism in platelets, Leukotriene C4 (LTC4) is the parent cysteinyl
leukotriene formed by the LTC4 synthase-catalyzed conjugation of
glutathione to LTA4. It is one of the constituents of slow-reacting
substance of anaphylaxis (SRS-A) and exhibits potent smooth muscle
contracting activity. LTC4, however, is rapidly metabolized to LTD4 and
LTE4, which makes the characterization of LTC4 pharmacology difficult.
N-methyl LTC4 is a synthetic analog of LTC4 that is not readily
metabolized to LTD4 and LTE4. Although the addition of the methyl group
blocks metabolism, the biological properties of N-methyl LTC4 are
somewhat reduced compared to that of LTC4. N-methyl LTC4 has a 30-fold
reduced binding to LTC4 receptor-expressing DMSO-differentiated U937
cell membranes compared to LTC4 (Ki =,486 versus 50 nM, respectively). |
|
N-nonanoyl-L-Homoserine lactone |
CAY-16868 |
|
|
|
Quorum sensing is a
regulatory system used by bacteria for controlling gene expression in
response to increasing cell density. This regulatory process manifests
itself with a variety of phenotypes including biofilm formation and
virulence factor production. Coordinated gene expression is achieved by
the production, release, and detection of small diffusible signal
molecules called autoinducers. The N-acylated homoserine lactones (AHLs)
comprise one such class of autoinducers, each of which generally
consists of a fatty acid coupled with homoserine lactone (HSL).
Regulation of bacterial quorum sensing signaling systems to inhibit
pathogenesis represents a new approach to antimicrobial therapy in the
treatment of infectious diseases. AHLs vary in acyl group length
(C4-C18), in the substitution of C3 (hydrogen, hydroxyl, or oxo group),
and in the presence or absence of one or more carbon-carbon double bonds
in the fatty acid chain. These
differences confer signal specificity through the affinity of
transcriptional regulators of the LuxR family.
C9-(L)-HSL is a rare odd-numbered acyl carbon chain produced by
wild-type Erwinia carotovora strain SCC 3193 grown in the nutrient-rich
Luria-Bertani Broth (LB) medium. |
|
N-octadecanoyl-L-Homoserine lactone |
CAY-13209 |
|
|
|
Quorum sensing is a
regulatory system used by bacteria for controlling gene expression in
response to increasing cell density. This regulatory process manifests
itself with a variety of phenotypes including biofilm formation and
virulence factor production. Coordinated gene expression is achieved by
the production, release, and detection of small diffusible signal
molecules called autoinducers. The N-acylated homoserine lactones (AHLs)
comprise one such class of autoinducers, each of which generally
consists of a fatty acid coupled with homoserine lactone (HSL).
Regulation of bacterial quorum sensing signaling systems to
inhibit pathogenesis represents a new approach to antimicrobial therapy
in the treatment of infectious diseases. AHLs vary in acyl group length
(C4-C18), in the substitution of C3 (hydrogen, hydroxyl, or oxo group),
and in the presence or absence of one or more carbon-carbon double bonds
in the fatty acid chain. These differences confer signal specificity
through the affinity of transcriptional regulators of the LuxR family.
C18-(L)-HSL is one of four lipophilic, long acyl side-chain bearing AHLs
produced by the LuxI AHL synthase homolog SinI involved in
quorum-sensing signaling in strains of Sinorhizobium meliloti, a
nitrogen-fixing bacterial symbiont of the legume Medicago sativa.
C18-(L)-HSL and other hydrophobic AHLs tend to localize in relatively
lipophilic cellular environments of bacteria and cannot diffuse freely
through the cell membrane. The long-chain N-acylhomoserine lactones may
be exported from cells by efflux pumps or may be transported between
communicating cells by way of extracellular outer membrane vesicles. |
|
N
Octanoyl-L-Homoserine lactone |
CAY-10011199 |
|
|
|
Quorum sensing is a
regulatory system used by bacteria for controlling gene expression in
response to increasing cell density. Controlling bacterial infections by
quenching their quorum sensing systems is a promising field of study.
The expression of specific target genes, such as transcriptional
regulators belonging to the LuxIR family of proteins, is coordinated by
synthesis of diffusible acylhomoserine lactone (AHL) molecules.
N-octanoyl-L-Homoserin lactone (C8-HSL) is a small diffusible signaling
molecule involved in quorum sensing, thereby controlling gene expression
and affecting cellular metabolism. The applications of this molecule
include infection prevention and regulation of virulence in general and
in cystic fibrosis. |
|
N-Oleoyl-L-Serine |
CAY-13058 |
|
|
|
Bone mass and shape
is continuously remodeled by the concerted and balanced action of
osteoblasts (bone forming cells) and osteoclasts (bone-resorbing cells).
The endocannabinoid system plays an essential role in the maintenance of
normal bone mass via signaling through the CB2 receptor.
N-Oleoyl-L-serine is an endogenous lipid that has been reported to
stimulate bone formation and to inhibit bone resorption. |
|
Nonacosadiene (7Z,11Z) |
CAY-9000314 |
|
|
|
Unsaturated cuticular
hydrocarbons serve as pheromones in insects. In D. melanogaster, these
hydrocarbons are sexually dimorphic in both their occurrence and their
effects. Nonacosadiene (7Z,11Z) is a cuticular pheromone in female fruit
flies that stimulates male courtship behavior. The biosynthesis of this
C29 diene appears to be mediated by an elongase with female-based
expression. |
|
N-pentadecanoyl-L-Homoserine lactone |
CAY-13094 |
|
|
|
Quorum sensing is a
regulatory system used by bacteria for controlling gene expression in
response to increasing cell density. This regulatory process manifests
itself with a variety of phenotypes including biofilm formation and
virulence factor production. Coordinated gene expression is achieved by
the production, release, and detection of small diffusible signal
molecules called autoinducers. The N-acylated homoserine lactones (AHLs)
comprise one such class of autoinducers, each of which generally
consists of a fatty acid coupled with homoserine lactone (HSL).
Regulation of bacterial quorum sensing signaling systems to inhibit
pathogenesis represents a new approach to antimicrobial therapy in the
treatment of infectious diseases. AHLs vary in acyl group length
(C4-C18), in the substitution of C3 (hydrogen, hydroxyl, or oxo group),
and in the presence or absence of one or more carbon-carbon double bonds
in the fatty acid chain. These differences confer signal specificity
through the affinity of transcriptional regulators of the LuxR family.
C15-HSL is a product of Y. pseudituberculosis. |
|
NSC 210902 |
CAY-10011255 |
|
|
|
Casein Kinase-2 (CK2)
is a serine/threonine-selective protein kinase involved in many signal
transduction pathways. CK2 is known to negatively regulate apoptosis,
and its activity is increased in many proliferating tissues and tumors,
which lends promise as an anticancer drug target. NSC210902 inhibits CK2
with an IC50 value of 1 M and competitively inhibits binding of ATP with
a Ki value of 0.28 M. NSC210902 is selective for CK2 as it only
minimally inhibits the activities of other protein kinases (e.g., JNK3,
GSK3, CDK5, and MSK1). |
|
N-tetradecanoyl-L-Homoserine Lactone |
CAY-10011200 |
|
|
|
Quorum sensing is a
regulatory system used by bacteria for controlling gene expression in
response to increasing cell density. Controlling bacterial infections by
quenching their quorum sensing systems is a promising field of study.
The expression of specific target genes, such as transcriptional
regulators belonging to the LuxR family of proteins, is coordinated by
the synthesis of diffusible acylhomoserine lactone (AHL) molecules.
N-tetradecanoyl-L-Homoserine lactone (C14-HSL) is a small diffusible
signaling molecule involved in quorum sensing, thereby controlling gene
expression and affecting cellular metabolism in bacteria. It appears
later than shorter acyl chain AHLs in developing biofilms and, like
other long chain AHLs, stimulates bacterial growth. C14-HSL also alters
the proteolytic activity and enhances the migration of some strains of
Proteus mirabilis. |
|
N-tridecanoyl-L-Homserine lactone |
CAY-13093 |
|
|
|
Quorum sensing is a
regulatory system used by bacteria for controlling gene expression in
response to increasing cell density. This regulatory process manifests
itself with a variety of phenotypes including biofilm formation and
virulence factor production. Coordinated gene expression is achieved by
the production, release, and detection of small diffusible signal
molecules called autoinducers. The N-acylated homoserine lactones (AHLs)
comprise one such class of autoinducers, each of which generally
consists of a fatty acid coupled with homoserine lactone (HSL).
Regulation of bacterial quorum sensing signaling systems to inhibit
pathogenesis represents a new approach to antimicrobial therapy in the
treatment of infectious diseases. AHLs vary in acyl group length
(C4-C18), in the substitution of C3 (hydrogen, hydroxyl, or oxo group),
and in the presence or absence of one or more carbon-carbon double bonds
in the fatty acid chain. These differences confer signal specificity
through the affinity of transcriptional regulators of the LuxR family.
N-tridecanoyl-L-Homoserine lactone (C13-HSL) possesses a rare
odd-numbered acyl carbon chain and is produced by wild-type and mutant
strains of Y. pseudotuberculosis in trace amounts. |
|
N-undecanoyl-L-Homoserine lactone |
CAY-16827 |
|
|
|
Quorum sensing is a
regulatory system used by bacteria for controlling gene expression in
response to increasing cell density. This regulatory process manifests
itself with a variety of phenotypes including biofilm formation and
virulence factor production. Coordinated gene expression is achieved by
the production, release, and detection of small diffusible signal
molecules called autoinducers. The N-acylated homoserine lactones (AHLs)
comprise one such class of autoinducers, each of which generally
consists of a fatty acid coupled with homoserine lactone (HSL).
Regulation of bacterial quorum sensing signaling systems to inhibit
pathogenesis represents a new approach to antimicrobial therapy in the
treatment of infectious diseases. AHLs vary in acyl group length
(C4-C18), in the substitution of C3 (hydrogen, hydroxyl, or oxo group),
and in the presence or absence of one or more carbon-carbon double bonds
in the fatty acid chain. These differences confer signal specificity
through the affinity of transcriptional regulators of the LuxR family.
C11-HSL possesses a rare odd-numbered acyl carbon chain and may be a
minor quorum-sensing signaling molecule in P. aeruginosa strains. |
|
p53 Cell-Based
Activation/Translocation Assay Kit |
CAY-600008 |
|
|
|
The tumor suppressor
protein p53 plays a crucial role in coordinating cellular responses to
genotoxic stress and holds many important clinical implications in the
treatment of cancer. Cayman's p53 Cell-Based Activation/Translocation
Assay Kit provides a highly specific p53 primary monoclonal antibody
together with a DyLightTM (product of Pierce Biotechnology, Inc.)
conjugated secondary antibody in a ready-to-use format. (-)-Nutlin-3, a
potent inhibitor of Mdm2-p53 interaction, which has been shown by
scientists at Cayman to cause the activation and translocation of p53
between the cytoplasm and nuclear compartments, is included as a
positive control. |
|
p53 Designer
Transcription Factor Assay Kit |
CAY-600030 |
|
|
|
The tumor suppressor
protein p53 is a transcription factor that plays a crucial role in
coordinating cellular responses to genotoxic stress and holds many
important clinical implications in the treatment of cancer. Caymans p53
Designer Transcription Factor Assay is designed to study alternate p53
DNA-binding sites. A biotinylated oligonucleotide is incubated with p53
contained in a nuclear extract; this mixture then binds to the
streptavidin plate provided in the kit. p53 is detected by addition of a
specific primary antibody directed against p53. A secondary antibody
conjugated to HRP is added to provide a sensitive colorimetric readout
at 450 nm. |
|
p53 Total and p53
(Phospho-Ser392) Dual Staining Assay Kit |
CAY-600060 |
|
|
|
The tumor suppressor
protein p53 plays a crucial role in coordinating cellular responses to
genotoxic stress and holds many important clinical implications in the
treatment of cancer. Cayman's p53 Total and p53 (Phospho-Ser392) Dual
Staining Assay Kit provides a pair of highly specific antibodies against
total and phospho-p53 (Phospho-Ser392) together with a pair of matched
DyLightTM (product of Pierce Biotechnology, Inc.) conjugated secondary
antibodies in a ready-to-use format. (-)-Nutlin-3, a potent inhibitor of
Mdm2-p53 interaction which has been shown to cause the activation and
translocation of p53 between the cytoplasm and nuclear compartments, is
included as a positive control. |
|
p53 Transcription
Factor Assay Kit |
CAY-600020 |
|
|
|
The tumor suppressor
protein p53 plays a crucial role in coordinating cellular responses to
genotoxic stress and holds many important clinical implications in the
treatment of cancer. Caymans p53 Transcription Factor Assay is a
non-radioactive, sensitive method for detecting specific transcription
factor DNA binding activity in nuclear extracts. A specific double
stranded DNA (dsDNA) sequence containing the p53 response element is
immobilized onto the wells of a 96-well plate. p53 contained in a
nuclear extract, binds specifically to the p53 response element and is
detected by addition of a specific primary antibody directed against
p53. A secondary antibody conjugated to HRP is added to provide a
sensitive colorimetric readout at 450 nm. |
|
Palmitoleic Acid |
CAY-10009871 |
|
|
|
Palmitoleic acid is
an omega-7 monounsaturated fatty acid that is a common constituent of
the triglycerides of human adipose tissue. It is found mainly in animal
fats, particularly in fish and marine mammals, and is also present in
the seeds of plants of the Proteaceae family. In contrast to a diet
enriched with oleic acid, palmitoleic acid-based diets raise low-density
lipoprotein (LDL) cholesterol and lower high-density lipoprotein (HDL)
cholesterol much like that of a saturated fatty acid, even when dietary
intake of cholesterol is maintained at a low level. |
|
Papaverine |
CAY-10011133 |
|
|
|
Papaverine is an
opium alkaloid that is structurally and pharmacologically distinct from
opiates. At the cellular level, papaverine inhibits phosphodiesterase
activity (IC50 = 13 M). Through this action, it increases cellular cAMP
levels and alters cellular function.
It has been shown to reduce arterial and cerebral vasospasm and
has been used to treat erectile dysfunction. Papaverine is recommended
as a potent nonselective phosphodiesterase inhibitor for in vitro and in
vivo research purposes. |
|
PCSK9 Monoclonal
Antibody (Clone 15A6) |
CAY-10218 |
|
|
|
Proprotein convertase
subtilisin kexin 9 (PCSK9) is a member of the subtilisin serine protease
family with an important role in lipoprotein metabolism.
Gain-of-function mutations in the PCSK9 gene are associated with
autosomal dominant hypercholesterolemia which is characterized by an
increase in lowdensity lipoprotein (LDL) cholesterol levels. PCSK9
overexpression in wild-type mice doubles the plasma total cholesterol,
possibly through acceleration of the degradation of the LDL receptor.
PCSK9 mRNA is detected in various tissues such as liver, kidney, lung,
spleen, jejunum, ileum, colon, and muscle with the highest expression in
the liver. Human PCSK9 precursor is 692 amino acids in length with an
estimated molecular weight of 74 kDa. This proprotein is self-cleaved to
form a mature protein at around 63 kDa in the Golgi. |
|
PD 0325901 |
CAY-13034 |
|
|
|
The dual specific
threonine/tyrosine kinase MEK is a key component of the RAS/RAF/MEK/ERK
signaling pathway that is frequently activated in human tumors. PD
0325901 is a potent MEK inhibitor that suppresses phosphorylation of ERK
in murine colon 26 tumors with an IC50 value of 0.33 nM. Suppression of
ERK activation with 1 M PD 0325901 combined with 3 M CHIR99021 (a
glycogen synthase kinase-3 inhibitor) prevents cell differentiation and
sustains self renewal of murine embryonic stem cells for at least eight
passages. |
|
PD 146176 |
CAY-10010518 |
|
|
|
PD 146176 is a potent
and selective inhibitor of reticulocyte 15-lipoxygenase-1. It limits
hypercholesterolemia-induced atherosclerosis in New Zealand White
rabbits and reduces oxidant
stress-induced apoptosis in endothelial cells. PD 146176 inhibits
amyloid β protein aggregate formation without changing total levels of
amyloid β precursor protein (APP) in cells stably expressing APP. In
addition, it lacks significant non-specific antioxidant properties. |
|
PD 184161 |
CAY-10012431 |
|
|
|
PD 184161 is a potent
and selective inhibitor of MEK1/2 with an IC50 value that ranges from
10-100 nM. More effective at inhibiting phosphorylation of ERK1/2 than
the selective MEK inhibitors, PD098059 and U0126, PD 184161 is useful
both in vitro and in vivo for studying the pharmacological role of the
Raf/MEK/ERK pathway. PD 184161 is structurally related to
clinically-studied MEK inhibitors PD184352 (CI-1040) and PD325901 and
has been shown to inhibit cell proliferation, induce apoptosis, and
possess antitumor activity in MEK-dependent cancers. |
|
PDI Polyclonal Antibody |
CAY-13025 |
|
|
|
The three dimensional
structure of many extracellular proteins is stabilized by the formation
of disulphide bonds. Studies suggest that a microsomal enzyme known as
protein disulphide isomerase (PDI) is involved in disulphide-bond
formation via its oxidase activity and isomerization via its isomerase
activity, as well as the reduction of disulphite bonds in proteins.
Studies suggest BiP and PDI work together sequentially to increase
oxidation of these proteins. PDI has also been found to function as a
chaperone to prevent the aggregation of unfolded substrates, serves as a
subunit of prolyl 4-hydroxylase and microsomal triglyceride transferase.
PDI is an abundant 55 kDa protein located primarily in the ER, however
studies have also proved its presence in the cytosol. PDI has the
ability to reside in the ER permanently due to the highly conserved KDEL
sequence at its carboxy-terminus. It uses carboxy-terminal KDEL as a
retention signal, and this appears to be sufficient to reduce the
secretion of proteins from the ER. This retention is reported to be
mediated by KDEL receptor. |
|
Phagocytosis Assay
Kit (IgG FITC) |
CAY-500290 |
|
|
|
Phagocytosis is a
very important physiological process which is characterized by the
ingestion of foreign particles and killing of microorganisms by
phagocytic leukocytes (granulocytes, monocytes, and macrophages). It
provides a first line of host defense against potential pathogens.
Phagocytosis is used as a model of microbe-innate immune interactions,
resulting in increased understanding of the consequences of these
interactions. Phagocytosis involves a complex series of events including
cytoskeletal rearrangement, alterations in membrane trafficking,
activation of microbial killing mechanisms, production of pro- and
anti-inflammatory cytokines and chemokines, activation of apoptosis, and
production of molecules required for efficient antigen presentation to
the adaptive immune system. Aberrant phagocytosis has been implicated in
several pathological conditions, such as Multiple Sclerosis, Alzheimers
disease, and atherosclerosis. Deficiencies in phagocytosis cause severe
and recurrent bacterial and fungal infections in affected individuals.
There are a variety of assays available to study the regulation and
mechanism of phagocytosis in vitro. Over time, these assays have changed
in nature. There were assays employing microscopy to directly visualize
engulfed particles, spectrophotometric evaluation of phagocytized
paraffin droplets containing dye, or scintillation counting of
radiolabeled bacteria. More recently developed assays use
fluorescently-opsonized latex beads or fluorescently-labeled bacteria
followed by flow cytometric analysis to assess the degree of
phagocytosis. The flow cytometric assay has an advantage of rapid
analysis of thousands of cells and quantification of internalized
particle density for each analyzed cell. Thus, the degree of
phagocytosis from cells treated with different compounds can be compared
quantifiably. Caymans Phagocytosis Assay Kit (IgG FITC) employs latex
beads coated with fluorescently-labeled rabbit-IgG as a probe for the
identification of factors regulating the phagocytic process in vitro.
The engulfed fluorescent-beads can be detected using a microscope
capable of measuring excitation and emission at 485 and 535 nm,
respectively, or be analyzed by a flow cytometer capable of excitation
at 488 nm. |
|
Phytanoyl-CoA
(triethylammonium salt) |
CAY-10011499 |
|
|
|
Phytanic acid is a
saturated 20-carbon branched-chain fatty acid that can only be derived
from dietary sources. Under normal conditions, phytanic acid is degraded
via α-oxidation (oxidative decarboxylation) to produce pristanic acid,
which then undergoes β-oxidation as part of the metabolism process.
Degradation of phytanic acid is impaired in patients with peroxisomal
disorders or diseases such as infantile phytanic acid storage disease or
Refsums disease. Phytanoyl-CoA is the conjugate of phytanic acid and
co-enzyme A (CoA). |
|
Phytomonic Acid |
CAY-10012556 |
|
|
|
Phytomonic acid is a
saturated fatty acid found mainly in a gram-negative bacteria, L.
arabinosus, but also in protozoa and in the seed oil of B. coccineus
(Connaraceae). Its cyclopropane ring structure has some properties of a
double bond, and it may serve to regulate cell membrane fluidity. |
|
Plerixafor (hydrochloride) |
CAY-10011332 |
|
|
|
The a-chemokine
receptor, CXCR4, on CD4+ T-cells is used by CXCR4-selective HIV forms as
a gateway for T-cell infection. In mammalian cell signaling, CXCR4
activation promotes the homing of hematopoietic stem cells, chemotaxis
and quiescence of lymphocytes, and growth and metastasis of certain
cancer cell types. Plerixafor (hydrochloride) is a macrocyclic compound
that acts as an irreversible antagonist against the binding of CXCR4
with its ligand, SDF-1 (CXCL12). It suppresses infection by HIV with an
IC50 value of 1-10 ng/ml with selectivity toward CXCR4-tropic virus.
Plerixafor mobilizes hematopoietic stem and progenitor cells for
transplant better than the 'gold standard', G-CSF, alone
and synergizes with G-CSF. It also increases T-cell trafficking
in the blood and spleen as well as the central nervous system.
Plerixafor also regulates the growth of primary and metastic breast
cancer cells and inhibits dissemination of ovarian carcinoma cells. |
|
Programmed Cell Death
Protein 4 (C-Term) Polyclonal Antibody |
CAY-10250 |
|
|
|
Programmed cell death protein 4 (PDCD4) levels are elevated during
apoptosis and absent in many cancer samples. Loss of PDCD4 expression is
an important event in cancer cell progression whereas the restoration of
PDCD4 protein can lower metalloproteinase activity and possible
metastasis. The known isoforms of PDCD4 differ only at the N-termini
with isoform 1 comprised of 468 amino acids and isoform 2 comprised of
458 amino acids. Each isoform contains two MA-3 domains essential for
binding of PDCD4 binding to eIF4A, thereby suppressing cell cycle
regulation and growth factor production. This antibody is capable of
detecting both PDCD4 isoforms. Additional protein modifications are
possible and can explain the range of masses detected by immunoblotting
(52-64 kDa). The molecular mechanisms of PDCD4 influence on tumor
suppression are becoming known but warrant further research. |
|
Prostaglandin B2
Lipid Maps MS Standard |
CAY-10007201 |
|
|
|
PGB2 is a
non-enzymatic dehydration product resulting from the treatment of PGE2
or PGA2 with strong base. It has weak agonist activity on TP receptors
and can increase pulmonary blood pressure in the rabbit at relatively
high doses (5 g/kg). |
|
Prostaglandin D
Synthase (hematopoietic-type) FP-Based Inhibitor Screening Assay Kit -
Green |
CAY-600007 |
|
|
|
Prostaglandin D2
(PGD2) is synthesized by hematopoietic-type PGD-synthase (H-PGDS) in
mast cells and is released in large quantities during allergic and
asthmatic anaphylaxis. H-PGDS is therefore a key target
for development of selective, potent inhibitors for therapeutic
use against these diseases. Caymans H-PGDS FP-Based Inhibitor Screening
Assay Kit - Green provides a rapid, accurate assay for screening H-PGDS
inhibitors. In this assay, a H-PGDS inhibitor-fluorescein conjugate
serves as a specific fluorescent probe for the enzyme. Displacement of
the probe by any unlabeled H-PGDS inhibitor leads to a decrease in the
fluorescence polarization (FP) state of the probe, providing a direct
signal for binding of the inhibitor to the active site of the enzyme.
This assay is robust (Z of 0.75) and eliminates the need for the
traditional multistep assay that requires the use of highly unstable
PGH2. The assay has been validated using several known inhibitors of
H-PGDS with IC50 values ranging from nanomolar to millimolar
concentrations. |
|
Prostaglandin D2
Ethanolamide Lipid Maps MS Standard |
CAY-10007203 |
|
|
|
Anandamide (AEA) is a
substrate for cyclooxygenase and the conversion of this fatty acid amide
to PGE2 compounds has been demonstrated in vitro. Conversion into any of
the other primary PGs is also theoretically possible. In addition, these
compounds are intresting analogs of the parent PG and may have useful
pharmacologic uses. PGD2-EA is one of these analogs. |
|
Prostaglandin D2
Lipid Maps MS Standard |
CAY-10007202 |
|
|
|
Prostaglandin D2
(PGD2) is a biologically active primary PG and a common product of
arachidonic metabolism in mammals. PGD2 is the major eicosanoid product
of mast cells and is released in large quantities during allergic and
asthmatic anaphylaxis. Mastocytosis patients produce excessive amounts
of PGD2, which causes vasodilation, flushing, hypotension, and syncopal
episodes. PGD2 is also produced in the brain via an alternative pathway
involving a soluble, secreted PGD-synthase also known as β-trace. In the
brain, PGD2 produces normal physiological sleep and lowering of body
temperature. Further pharmacological actions include inhibition of
platelet aggregation and relaxation of vascular smooth muscle. PGD2
inhibits human ovarian tumor cell proliferation with an IC50 value of
6.8 M. |
|
Prostaglandin E Synthase (cytosolic, FL) Polyclonal Antibody |
CAY-10209 |
|
|
|
Cytosolic PGE synthase (cPGES) is a glutathione-dependent enzyme with a
predicted size of 18.6 kDa (23 kDa on SDS-PAGE). The enzyme is expressed
in a wide variety of tissues and cells, the levels of which are
unaffected by treatment with IL-1β and TNFα. However, enzyme expression
increases approximately 3-fold in rat brain following LPS treatment.
Microsomal PGE synthase (mPGES) is a 16 kDa protein expressed in a
variety of tissues. In contrast to cPGES, mPGES protein expression is
increases in A549 cells following treatment with IL-1β. The two enzymes
show <10% homology at the amino acid level. |
|
Prostaglandin E Synthase-1 (microsomal) (human recombinant) |
CAY-10007939 |
|
|
|
Prostaglandin E synthases (PGESs) are enzymes that convert
cyclooxygenase (COX)-derived PGH2 to PGE2. There are three different
PGES enzymes with distinct enzymatic properties, modes of expression,
cellular and subcellular localizations, and intracellular functions, two
of which are membrane-bound enzymes and have been designated as mPGES-1
and mPGES-2. mPGES-1 is a
perinuclear protein belonging to the membrane-associated proteins
involved in eicosanoid and glutathione metabolism (MAPEG) superfamily.
It requires glutathione as an essential cofactor for activity. mPGES-1
is up-regulated in response to various proinflammatory stimuli with a
concomitant increased expression of COX-2 and is down-regulated by
glucocorticoids. mPGES-1 gene knockout studies in mice have indicated
the role of mPGES-1 generated PGE2 in female reproduction, inflammation,
pain, fever, anorexia, atherosclerosis, stroke, and tumorigenesis.
Therefore, mPGES-1 is a potential drug target for various
diseases. |
|
Prostaglandin E2
Lipid Maps MS Standard |
CAY-10007211 |
|
|
|
Prostaglandin E2
(PGE2) is one of the primary COX products of arachidonic acid and one of
the most widely investigated prostaglandins. Its activity influences
inflammation, fertility and parturition, gastric mucosal integrity, and
immune modulation. The effects of PGE2 are transduced by at least four
distinct receptors designated EP1, EP2, EP3, and EP4. Affinity constants
(Kd) of PGE2 for these receptors range from 1-10 nM depending on the
receptor subtype and tissue. |
|
Prostaglandin
E2-PEG11-Biotinamide |
CAY-9000376 |
|
|
|
PGE2 is the major
eicosanoid product of cyclooxygenase-1 and 2 in epithelial cells,
leukocytes, reproductive tissues, and many others. PGE2 contracts smooth
muscle, protects the gastric mucosa, modulates immune function, and
regulates fertility and implantation. PGE2 acts through at least four
G-protein coupled receptors, EP1 -EP4. PGE2-PEG11-biotinamide is an
affinity probe which allows PGE2 to be detected or immobilized using the
biotin ligand. The PEG11 spacer serves to separate the biotin linker
from PGE2 with a hydrophilic spacer.
It is thus a tool to be used in the elucidation of PGE2 actions
or interactions in aqueous solutions. |
|
Prostaglandin F2.alpha. Ethanolamide Lipid Maps MS Standard |
CAY-10007222 |
|
|
|
Prostaglandin F2α ethanolamide (PGF2α-EA) is produced by cyclooxygenase
2 (COX-2) metabolism of the endogenous cannabinoid, arachidonoyl
ethanolamide (AEA), found in brain, liver, and other mammalian tissues.
AEA can be used directly by the sequential action of COX-2 and specific
PG synthases to produce ethanolamide congeners of the classical PGs.
PGF2α-EA has also been reported to be biosynthesized by this mechanism
when AEA was infused into the lung and liver of living mice. PGF2α-EA is
a potent dilator (EC50 = 58 nM) of the cat iris sphincter, which is a
model system for testing potential intraocular hypotensive agents. |
|
Prostaglandin F2β
Lipid Maps MS Standard |
CAY-10007232 |
|
|
|
Prostaglandin F2β
(PGF2β) is the 9β-hydroxy stereoisomer of PGF2α. It is much less active
than PGF2α in antifertility and bronchoconstrictor activities. PGF2β
exhibits bronchodilating activity in guinea pigs and cats and
antagonizes the bronchoconstrictor activity of PGF2α. |
|
Prostaglandin K2
Lipid Maps MS Standard |
CAY-10007236 |
|
|
|
Prostaglandin K2
(PGK2) is the 9,11-diketone formed by the oxidation of PGE2 or PGD2.
Whether this compound exists biologically is uncertain; it is known to
be resistant to metabolism by 15-hydroxy PGDH in vitro. |
|
Prostratin |
CAY-10272 |
|
|
|
Prostratin is a
non-tumor promoting phorbol ester that potently induces HIV-1
reactivation in latent reservoirs of infected Jurkat-LAT-GFP cells with
an IC50 value of ~ 0.5 M. Originally, prostratin was isolated from
plant sources including Pimelea prostrata, Euphorbia cornigera, and
Hoalanthus nutans. The effects of prostratin are mediated through
activation of NF-κB via protein kinase C and by downregulation of HIV-1
receptor CD4 expression and its co-receptors CXCR4 and CCR5. |
|
Protein Tyrosine
Phosphatase 1b (human recombinant) |
CAY-10010896 |
|
|
|
Protein tyrosine
phosphatase (PTPs) are an enzyme superfamily that includes about 100
human proteins. Their function is to remove phosphate from tyrosine
residues of cellular proteins. Reversible phosphorylation catalyzed by
the coordinated actions of protein tyrosine kinases and phosphatases is
of paramount importance to the regulation of the signaling events that
underlie such fundamental processes as growth and proliferation,
differentiation, and survival or apoptosis, as well as adhesion and
motility. One of the most heavily studied PTP proteins is PTP1B. Data
suggests PTP1B is a negative regulator in both insulin and leptin
signaling. As such, PTP1B has become a leading diabetes target. |
|
Protocatechuate Dioxygenase |
CAY-10011353 |
|
|
|
Protocatechuate
dioxygenase (PCD) catalyzes the proximal extradiol ring cleavage of
protocatechuate (PCA) with attendant incorporation of both atoms of
oxygen from O2. The PCD holoenzyme consists of α (23 kDa) and β (26.5
kDa) subunits, which form a tetramer with four ferric ions for a total
weight of ~200 kDa. Iron is essential for activity because the
substrate, PCA, initially binds directly to the iron through both
hydroxyl groups to form a chelate complex. PCD is an important component
of bacterial metabolism of aromatic compounds found in the soil.
However, many publications are now reporting the usefulness of the
PCD/PCA oxygen scrubbing (oxygen scavenging) system for maintaining
anaerobic experimental conditions. Caymans protocatechuate dioxygenase
is the 3,4-PCD expressed and purified from a bacterial overexpression
system. 3,4-PCD catalyzes the oxidative ring cleavage of
3,4-dihydroxybenzoate to produce β-carboxy-cis,cis-muconate. Activity of
the PCD can be measured by monitoring the rate of O2 uptake with an
oxygen electrode, or by measuring the amount of product
(β-carboxy-cis,cis-muconate) formed at 290 nm. |
|
PtdIns-(1-arachidonoyl, 2-arachidonoyl-d8) (sodium salt) |
CAY-9000305 |
|
|
|
PtdIns-(1-arachidonoyl, 2-arachidonoyl-d8) (sodium salt) is used as an
internal standard for the quantification of PtdIns-(1-arachidonoyl,
2-arachidonoyl) (sodium salt) by stable isotope dilution MS. The
accuracy of the sample weight in this vial is between 5% over and 2%
under the amount shown on the vial. If better precision is required, the
deuterated standard should be quantitated against a more precisely
weighed unlabeled standard by constructing a standard curve of peak
intensity ratios (deuterated versus unlabeled). The
phosphatidylinositols (PtdIns) represent a small percentage of total
membrane phospholipids. However, they play a critical role in the
generation and transmission of cellular signals. PtdIns-(1-arachidonoyl,
2-arachidonoyl-d8) (sodium salt) is a synthetic analog of natural PtdIns
featuring deuterated C20:4 fatty acids at the sn-1 and sn-2 positions.
This synthetic standard compound contains the same inositol and diacyl
glycerol (DAG) stereochemistry as that of the natural compound. |
|
PtdIns-(3,4,5)-P3 (1,2-dihexanoyl) (ammonium salt) |
CAY-10008390 |
|
|
|
The
phosphatidylinositol (PtdIns) phosphates represent a small percentage of
total membrane phospholipids. However, they play a critical role in the
generation and transmission of cellular signals.
PtdIns-(3,4,5)-P3, also known as PIP3, is resistant to cleavage
by PI-specific phospholipase C (PLC).
Thus, it is likely to function in signal transduction as a
modulator in its own right, rather than as a source of inositol
tetraphosphates. PIP3 can serve as an anchor for the binding of signal
transduction proteins bearing pleckstrin homology (PH) domains.
Protein binding to PIP3 is important for cytoskeletal
rearrangement and membrane trafficking. PtdIns-(3,4,5)-P3
(1,2-dihexanoyl) is a synthetic analog of natural PIP3 with saturated C6
fatty acids at the sn-1 and sn-2 positions. The compound features the
same inositol and diacylglycerol (DAG) stereochemistry as that of the
natural compound. The short fatty
acid chains of this analog give it different physical properties from
naturally-occurring PIP3, including higher solubility in aqueous media. |
|
PtdIns-(3,4,5)-P3
-fluorescein (ammonium salt) |
CAY-10010383 |
|
|
|
The
phosphatidylinositols (PtdIns) phosphates represent a small precentage
of total membrane phospholipids. However, they play a critical role in
the generation and transmission of cellular signals. PtdIns-(4,5)-P2 can
be phosphorylated by phosphatidylinositol (PI)-3-kinase to make
PtdIns-(3,4,5)-P3, which initiates an intricate signaling cascade that
has been implicated in cancer. PtdIns-(3,4,5)-P3 fluorescein is a
fluorescent probe for any protein with a high affinity binding
interaction with inositol-(3,4,5)-triphosphate phospholipids, such as
PI-3-kinase, PTEN, or PH-domain-containing proteins. |
|
PtdIns-(4,5)-P2-fluorescein (ammonium salt) |
CAY-10010388 |
|
|
|
The
phosphatidylinositol (PtdIns) phosphates represent a small percentage of
total membrane phospholipids. However, they play a critical role in the
generation and transmission of cellular signals.
PtdIns-(4,5)-P2-fluorescein is a fluorescent probe for any protein with
a high-affinity binding interaction with inositol-(4,5)-triphosphate
phospholipids, such as PI-3-kinase, PTEN, or PH-domain-containing
proteins. |
|
PTEN (human recombinant) |
CAY-10009746 |
|
|
|
Phosphatase and
tensin homology on chromosome 10 (PTEN) functions as a key regulatory
enzyme in many signal transduction pathways by dephosphorylating
proteins and lipids such as AKT and phosphatidylinositol
3,4,5-triphosphate (PIP3). PTEN interacts with many other proteins to
regulate cell division and migration, as well as promoting apoptosis
when necessary. Mutation of PTEN results in many human cancers including
melanoma and prostate carcinoma, making PTEN an important tumor
suppressor. PTEN is expressed in almost all tissues of the body as a 403
amino acid protein with an estimated molecular weight of 47 kDa, however
the actual migration observed on western blot may vary among distinct
samples. |
|
Pyrimidine-4-carboxylic Acid |
CAY-10010564 |
|
|
|
Pyrimidine-4-carboxylic acid is a synthetic intermediate useful for
pharmaceutical synthesis. |
|
QX-314 (bromide) |
CAY-10011032 |
|
|
|
QX-314 is a
membrane-impermeant lidocaine derivative that selectively blocks sodium
channels on nociceptive neurons when delivered intracellularly via the
TRPV1 channel, but is reportedly ineffective with extracellular
application. When supplied in combination with 1 M capsaicin, a TRPV1
receptor agonist, 5 mM QX-314 blocks 98% of sodium current in
voltage-clamped nociceptive DRG neurons. QX-314 elicits a long-lasting
decrease in the response to painful mechanical and thermal stimuli
without imparting the motor deficits (e.g., numbness, paralysis)
associated with many conventional local anesthetics. At concentrations
ranging from 10-70 mM, peripheral application of QX-314 dose-dependently
produces robust local anesthesia with slow onset in the guinea pig
intradermal wheal assay, the murine tail-flick test, and the murine
sciatic nerve blockade model. However, injection of 0.5-30 mM QX-314 in
the lumbar intrathecal space produces neurotoxicity and death in mice. |
|
Rabbit Anti-Mouse IgA
Polyclonal FITC |
CAY-10196 |
|
|
|
This rabbit
anti-mouse IgA FITC is used as the secondary antibody for immunostaining
experiments where the primary antibody is mouse IgA, such as Caymans
CD36 Monoclonal Antibody (Catalog No. 188150). Indirect immunostaining
may produce improved resolution of stained and unstained samples in
comparison to direct immunostaining with certain samples. For example,
indirect immunostaining may be more useful for analysis of rare cell
populations or with cells expressing low levels of the target molecule. |
|
Radicicol |
CAY-13089 |
|
|
|
Radicicol is a
natural product with antibiotic, antifungal, and antimalarial
properties. It binds and inhibits heat shock protein 90 (Hsp90) with
nanomolar affinity. This interaction inhibits p23 from associating with
Hsp90, suppresses signaling through HIF-1α, and produces decreased
levels of progesterone receptor, Raf-1, p185erb82, and mutant p53.
Radicicol also binds to, and inhibits, DNA topoisomerase type II
proteins and GRP94 through an ATPase domain common to Hsp90. |
|
Raloxifene (hydrochloride) |
CAY-10011620 |
|
|
|
Selective estrogen
receptor modulators (SERMs) are a class of pharmacologically active ER
ligands that exert agonist and antagonist effects on various estrogen
target tissues. They are designed to promote the beneficial actions of
estrogen (e.g., bone maintenance and remodeling) while preventing its
detrimental effects (e.g., growth of breast and endometrial cancers).
Raloxifene, marketed under the name Evista, is a SERM that exhibits
estrogenic activity in bone cells without stimulating breast or uterine
tissues. It has been approved for clinical use for prevention and
treatment of postmenopausal osteoporosis. When administered at 60 mg/day
for 12 weeks to postmenopausal, osteoporotic women, raloxifene reduced
bone resportion, and promoted bone formation by decreasing serum levels
of interleukin-6 and parathyroid hormone and increasing serum levels of
25-hydroxy vitamin D. Raloxifene reportedly guards endothelial cells
obtained from rat aortic rings against oxidative insult (1 M) and lowers
serum cholesterol in ovariectomized rodents (ED50 =.2 mg/kg). |
|
Rimonabant |
CAY-9000484 |
|
|
|
Rimonabant, also
known as SR141716, was the first selective central cannabinoid (CB1)
receptor inverse agonist (Ki = 1.8 nM) to be developed as an appetite
suppressant, anti-obesity drug. It is widely used as a tool to
investigate CB receptor properties and the mechanisms by which CB
agonists exert their pharmacological effects. In rodent models and
clinical trials, rimonabant effectively induces lipolysis, reduces
hepatomegaly, decreases body weight, and improves dyslipidemia by
reducing triglyceride, free fatty acid and total cholesterol levels and
by increasing HDL/LDL ratios. However, rimonabant reportedly produces
adverse psychiatric and neurological effects (e.g., depression or
anxiety) and therefore is not approved by the FDA for use as a weight
control medication. Rimonabant elicits antiproliferative and immunom
odulatory effects (e.g., cell cycle arrest, increased expression of IκB
and phosphorylated Akt, and decreased expression of NF-κB,
phosphorylated ERK 1/2, COX-2, and iNOS) in vitro. |
|
Rolipram |
CAY-10011132 |
|
|
|
Type 4 cyclic
nucleotide phosphodiesterases (PDE4) isoforms selectively inactivate the
second messenger cAMP by hydrolyzing the phosphodiester bond, producing
AMP. Rolipram is a cell-permeable selective PDE4 inhibitor. Since PDE4
is abundant in leukocytes, rolipram inhibits inflammation by suppressing
leukocyte function, inhibiting C5a-stimulated LTC4 synthesis in
eosinophils (IC50 = 200 nM), and lipopolysaccharide-induced TNF
synthesis in monocytes (IC50 = 360 nM). Rolipram also enhances neuronal
survival, has antipsychotic effects in mice, and suppresses bone loss in
ovariectomized rats. |
|
Salermide |
CAY-13178 |
|
|
|
The sirtuins (SIRTs)
are a family of NAD+-dependent histone deacetylases involved in gene
regulation that is relevant to, e.g., longevity, cancer, gene
regulation, energy homeostasis, and apoptosis. Salermide is an inhibitor
of SIRT1 and SIRT2, causing tumor-specific cell death through apoptosis.
In MOLT4 leukemia cells, salermide causes 90% apoptosis within 72
hours (IC50 ~ 20 M) by reactivating proapototic genes that are
repressed by SIRT1. |
|
SB 203580 |
CAY-13067 |
|
|
|
Mitogen-activated
protein kinases (MAPK) mediate signal transduction from cell surface
receptors to the nucleus and are classified into various subtypes. p38
MAPK is activated by environmental stresses and inflammatory cytokines
and is critical for normal immune and inflammatory responses as it
regulates the expression of many cytokines, transcription factors, and
cell surface receptors. SB 203580 is a pyridinyl imidazole inhibitor of
p38 MAPK that specifically blocks its kinase activity. SB 203580 does
not, however, disrupt JNK activity, which is activated by similar
stressors to those which activate p38 MAPK. p38 MAPK activity in
heat-shocked HeLa cells and osmotically stressed PC12 cells is inhibited
by SB 203580 with an IC50 value of 0.6 M. SB 203580 also prevents the
activation of PKB/Akt by inhibiting phosphoinositide-dependent protein
kinase 1 (PDK1) at IC50 values of 3-5 M. |
|
SB 415286 |
CAY-10010247 |
|
|
|
Glycogen synthase
kinase 3 (GSK3) is a serine/threonine protein kinase that is inhibited
by an assortment of extracellular stimuli such as insulin, growth
factors, cell specification factors, and cell adhesion. Its activity
regulates many cell functions including the control of cell division,
apoptosis, and inflammation. SB 415286 is a potent and selective
cell-permeable, ATP-competitive inhibitor of GSK3α with an IC50 value of
78 nM (similar potency for GSK3β) and a Ki value of 31 nM.
As a result of GSK3 inhibition, SB 415286 stimulates glycogen
synthesis in the Chang human liver cell line with an EC50 value of 2.9
M. SB 415286 also protects primary neurons from death induced by the
PI3-kinase pathway. |
|
Sclerotiorin |
CAY-89460 |
|
|
|
Sclerotiorin is a
natural product isolated primarily from Penicillium species. It inhibits
soybean lipoxygenase-1 with an IC50 value of 4.2 M. Sclerotiorin also
exhibits a number of other activities including inhibition of
cholesterol ester transfer protein (IC50 = 19.4 M), inhibition of
Grb2-Shc interaction (IC50 = 22 M), and antagonism of endothelin
receptors (IC50 = 114 and 152 M for human ETA and ETB, respectively). |
|
S-Glutathionylated
Protein Detection Kit |
CAY-10010721 |
|
|
|
Caymans
S-Glutathionylated Protein Detection Assay Kit provides a convenient
method for the direct visualization of S-glutathionylated proteins in
whole (permeabilized) cells by flow cytometry and microscopy as well as
avidin overlay analysis. This cell-based assay starts with the
modification of protein free-thiols groups followed by enzymatic
cleavage of any protein-S-glutathione (PSSG) adducts present in the
sample. Biotinylation of the newly-formed protein free-thiols provides
the basis for visualization using streptavidin-based colorimetric or
fluorescence detection. Reagents are provided to test three sets of 10
samples (most convenient) or up to thirty samples total at once if
desired. |
|
SIRT1 (human recombinant) |
CAY-10011190 |
|
|
|
The sirtuins
represent a distinct class or trichostatin A-insensitive
lysyl-deacetylases (class III HDACs) and have been shown to catalyze a
reaction that couples lysine deacetylation to the formation of
nicotinamide and O-acetyl-ADP-ribose from NAD+ and the abstracted acetyl
group. There are seven human sirtuins, which have been designated SIRT
1-7. SIRT 1, which is located in the nucleus, is the human sirtuin with
the greatest homology to yeast Sir2 (Silent information regulator 2) and
has been shown to regulate the activity of the p53 tumor suppressor and
inhibit apoptosis. These results have significant implications regarding
an important role of SIRT 1 in modulating the sensitivity of cells in
the p53-dependent apoptotic response and the possible effect in cancer
therapy. Since the growth suppressive function of p53 is strongly
enhanced by DNA damaging reagents, it is expected that inhibitors of
SIRT 1 may be effective anti-cancer drugs. |
|
SIRT3 (human recombinant) |
CAY-10011194 |
|
|
|
The sirtuins
represent a distinct class of trichostatin A-insensitive
lysyl-deacetylases (class III HDACs) and have been shown to catalyze a
reaction that couples lysine deacetylation to the formation of
nicotinamide and O-acetyl-ADP-ribose from NAD+ and the abstracted acetyl
group. There are seven human sirtuins, which have been designated SIRT
1-7. SIRT3, is a mitochondrial protein, with its N-terminal 25 amino
acid residues responsible for its localization. Synthesized as an
enzymatically inactive protein, human SIRT3 is activated by a
matrix-processing peptidase. Recently, it was demonstrated that SIRT3 is
translocated to the mitochondria from the nucleus during cellular stress
or by the overexpression of SIRT3 itself. (The expression of SIRT3 is
finely regulated.) In mice, caloric restriction up-regulates SIRT3
expression levels in white and brown adipose tissue (WAT & BAT). Cold
exposure also induces SIRT3 in brown adipose tissue (BAT). The
constitutive expression of SIRT3 promotes the expression of PGC-1a,
UCP1, and other genes involved in mitochondrial functions, indicating
that SIRT3 modulates adaptive thermogenesis in BAT. |
|
SIRT3 Direct
Fluorescent Screening Assay Kit |
CAY-10011566 |
|
|
|
The sirtuins
represent a distinct class of trichostatin A-insensitive
lysyl-deacetylases (class III HDACs) that catalyze a reaction coupling
lysine deacetylation to the formation of nicotinamide and
O-acetyl-ADP-ribose. SIRT3 is a mitochondrial protein that plays a role
in metabolic regulation and other cellular processes. It is the only
human sirtuin with a direct genetic link with longevity. Additional
research needs to be done to further elucidate the mechanism behind the
involvement of SIRT3 in metabolic dysfunction, aging, cancer, and
neurodegenerative disease. Cayman's SIRT3 Direct Fluorescent Screening
Assay Kit provides a convenient fluorescence-based method for screening
SIRT3 inhibitors or activators. The procedure requires only two easy
steps, both performed in the same microplate. In the first step, the
substrate, which comprises the p53 sequence
Gln-Pro-Lys-Lys(e-acetyl)-AMC, is incubated with human recombinant SIRT3
along with its cosubstrate NAD+. Deacetylation sensitizes the substrate
such that treatment with the developer in the second step releases a
fluorescent product. The fluorophore can be analyzed with an excitation
wavelength of 350-360 nm and an emission wavelength of 450-465 nm. |
|
Soluble Epoxide
Hydrolase Cell-Based Assay Kit |
CAY-600090 |
|
|
|
Mammalian soluble
epoxide hydrolase (sEH) is a member of the α/β-hydrolase fold family of
enzymes that catalyze the hydrolysis of exogenous and endogenous
epoxides to vicinal diols. sEH is a homodimer consisting of two domains.
The C-terminal domain is responsible for the epoxide hydrolase activity
while the N-terminal domain has a catalytic center with phosphatase
activity. Endogenous substrates for sEH include epoxyeicosatrienoic
acids (EETs) which exhibit vasodilatory and anti-inflammatory activity.
Inhibition of sEH in animal models was shown to effectively treat
hypertension and vascular inflammation as well as related syndromes.
These studies demonstrate the value for targeting sEH for development of
small molecule inhibitors as therapeutics. Caymans sEH Cell-Based Assay
Kit provides a convenient 96-well plate, fluorescence-based method for
detecting epoxide hydrolase activity in whole cells. |
|
|
|
The assay utilizes
Epoxy Fluor 7, a sensitive fluorescent substrate for sEH that can be
used to monitor the activity of both human and murine enzymes.
Hydrolysis of the substrate epoxide yields a highly fluorescent product,
6-methoxy-2-Naphthaldehyde, that can be monitored at excitation and
emission wavelengths of 330 and 465 nm, respectively.
6-Methoxy-2-Naphthaldehyde is included to quantify enzyme activity and a
recombinant sEH is included as a positive control. An sEH inhibitor AUDA
is also included for checking specificity of the reaction. This assay
parallels Caymans Soluble Epoxide Hydrolase Inhibitor Screening Assay
Kit (Catalog No. 10011671) which uses recombinant protein rather than
whole cells for the assay. Together, both assays will help to identify
whether or not an inhibitor/activator has a direct or indirect effect on
the enzyme. |
|
Soluble Epoxide
Hydrolase Inhibitor Screening Assay Kit |
CAY-10011671 |
|
|
|
Soluble epoxide
hydrolase (sEH) catalyzes the hydrolysis of exogenous and endogenous
epoxides to vicinal diols. Endogenous substrates for sEH include
epoxyeicosatrienoic acids (EETs) which exhibit vasodialatory and
anti-inflammatory activity. Small molecule inhibitors of sEH may
therefore hold promise as therapeutics for the treatment of hypertension
and vascular inflammation. Cayman's fluorescence-based sEH Inhibitor
Screening Assay Kit provides a convenient method for screening epoxide
hydrolase inhibitors. The assay utilizes (3-phenyl-oxiranyl)-acetic acid
cyano-(6-methoxy-naphthalen-2-yl)-methyl ester (PHOME) as a substrate.
Hydrolysis of PHOME by epoxide hydrolase produces the highly fluorescent
6-methoxy-2-naphthaldehyde which can be analyzed using an excitation
wavelength of 330 nm and emission wavelength of 465 nm. Each kit
contains buffer, substrate, and sufficient human recombinant sEH for 100
tests. |
|
SP 600125 |
CAY-10010466 |
|
|
|
The three isoforms of
c-Jun N-terminal kinase (JNK) are members of the MAP kinase superfamily
that induce the expression of immediate-early genes in response to
specific stress and inflammatory signals. Through these actions, the JNK
enzymes modulate cell proliferation, apoptosis, differentiation, and
autophagy. SP 600125 is a potent and reversible inhibitor of JNK1, 2,
and 3, with an IC50 value of 0.11 μM. It is cell-permeable and
dose-dependently inhibits c-Jun phosphorylation in cells, blocking the
expression of COX-2 and TNF-α in monocytes and IL-10, TNF-α, and IFN-γ
in T-cells. SP 600125 also prevents apoptosis in many cell types,
including B cells, and inhibits autophagy in HeLa cells. |
|
-Hydroxybutyrate
(Ketone Body) Assay Kit |
CAY-700190 |
|
|
|
Caymans -HB (Ketone
Body) Assay Kit provides a simple, reproducible, and sensitive tool for
measuring -HB levels in plasma, serum, or urine. The method for -HB
determination is based upon the oxidation of D-3-Hydroxybutyrate to
acetoacetate by the enzyme 3-hydroxybutyrate dehydrogenase. Concomitant
with this oxidation, the cofactor NAD+ is reduced to NADH. In the
presence of diaphorase, NADH reacts with the colorimetric detector WST-1
to produce a formazan dye with an absorbance maximum at 445-455 nm. The
absorbance of the dye is directly proportional to the -HB
concentration. |
|
Stearic Acid |
CAY-10011298 |
|
|
|
Stearic acid is a
long-chain saturated fatty acid that can be derived from either animal
fats or vegetable oils. Compared to other long-chain saturated fatty
acids that are hypercholesterolemic
experimental diets high in stearic acid (9.3-11.8% of energy) do
not raise plasma total cholesterol or LDL-cholesterol
concentrations but may slightly reduce HDL-cholesterol
concentrations. Stearic acid can be used as a hardening agent for
vegetable oils and due to its negligible effect on cholesterol
metabolism may be used as an alternative to modification of fatty acids
by partial hydrogenation. |
|
Swainsonine |
CAY-16860 |
|
|
|
Swainsonine is an
indolizidine alkaloid naturally found in certain plants that inhibits
N-linked glycoside hydrolases, preventing the processing of
asparagine-linked glycoproteins. It reversibly inhibits lysosomal
α-mannosidase and Golgi α-mannosidase II (IC50 = 0.2 μM). Swainsonine is
used to study the role of N-linked glycosylation in cellular processes
and has been shown to have antiproliferative and antimetastatic effects
of cancer cells in culture and in mice. The inhibition of α-mannosidase
activity in lysosomes produces an accumulation of partially-processed
oligosaccharides and glycoproteins, giving rise to lysosomal storage
disease. Swainsonine toxicity in herbivores results in a condition known
as locoism, characterized by hyperactivity, aggression, stiff and clumsy
gait, low head carriage, salivation, seizures, and apparent blindness,
culminating in increased miscoordination, weakness and death. |
|
TAF 10 Peptide |
CAY-10228 |
|
|
|
TAF10 is one of many
protein factors or coactivators associated with RNA polymerase II
activity. One vial of this peptide may be used as a methyltransferase
acceptor peptide for more than 200 reactions at 15 M. |
|
Tangeritin |
CAY-10009911 |
|
|
|
Tangeritin is a
polymethoxylated flavone isolated from peels of citrus fruits. It
inhibits signaling in cancer cells, reducing ERK phosphorylation and
growth of estradiol-stimulated T47D breast cancer cells (IC50 ~ 3 μM)
and blocking p38 MAPK, JNK, and AKT activation in IL-1β-stimulated human
lung carcinoma A549 cells. Tangeritin also activates the pregnane X
receptor, inducing MDR1 expression in human colonic LS180 cancer cells
at a concentration of 10 μM and inhibits growth of tumors and tumor
implantation in lungs of mice inoculated with murine melanoma B16F10
cells. It also protects against tunicamycin-induced cell death in
isolated mouse insulinoma MIN6 cells and in renal tubular epithelium in
mice at a concentration of 10 μM. More recently, tangeritin has been
shown to significantly reduce serum total and LDL cholesterol and
triacylglycerols in hypercholesteremic hamsters. |
|
Tenovin-1 |
CAY-13085 |
|
|
|
Tenovin-1 is a small
molecule activator of p53 transcriptional activity. At 10 M, it elevates
p53 expression in MCF-7 cells within two hours of treatment and
longer-term exposure significantly decreases the growth of BL2 Burkitts
lymphoma and ARN8 melanoma cells. Functioning upstream of p53, tenovin-1
acts by inhibiting the deacetylase activity of purified human SIRT1 and
SIRT2, members of NAD+-dependent class III histone deacetylases that
belong to the sirtuin family. While tenovin-1 demonstrates low
genotoxicity, the compound has poor water solubility, which limits its
uses in vivo. |
|
Tenovin-6 |
CAY-13086 |
|
|
|
The tumor suppressor
function of p53 hinges on its ability to function as a transcription
factor. Tenovin-6 is a water-soluble analog of tenovin-1, a small
molecule activator of p53 transcriptional activity. At 10 M, this
compound is slightly more effective than tenovin-1 at elevating p53
expression in MCF-7 cells and reduces growth of ARN8 melanoma xenograft
tumors in SCID mice at a dose of 50 mg/kg. Tenovin-6 inhibits the
protein deacetylase activities of purified human SIRT1, SIRT2, and SIRT3
in vitro with IC50 values of 21, 10, and 67 M, respectively. |
|
tetramethyl Nordihydroguaiaretic Acid |
CAY-70302 |
|
|
|
tetramethyl Nordihydroguaiaretic acid (TMNDGA) is a synthetic derivative
of NGDA. It inhibits HIV the transactivator and activity of the herpes
simplex virus (HSV) ICP4 gene promoter with IC50 values of 11 and 43.5 M
respectively. TMNDGA induces growth arrest and apoptosis by suppressing
Sp1-dependent Cdc2 and survivin gene expression giving rise to its
antitumorigenic activity. The in vivo growth of xenografts in numerous
human tumor types was suppressed upon treatment with TMNDGA. It also
inhibits the growth of murine and human melanomas and human colon cancer
in vivo without causing other tissue toxicity. TMNDGA is currently in
Phase I & II clinical trials for treatment of high grade glioma brain
tumors. |
|
tetranor-PGDM EIA Kit |
CAY-501001 |
|
|
|
Caymans
tetranor-PGDM EIA Kit is a competitive assay that can be used for
quantification of tetranor-PGDM in urine. The EIA typically displays an
IC50 (50% B/B0) of approximately 300 pg/ml and a detection limit (80%
B/B0) of approximately 55 pg/ml. |
|
Thioperamide Maleate |
