Phosphodiesterases
(PDE) &
Related Products
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Recombinant
PDEs (Phosphodiesterases] |
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PDE1A (human, recombinant, N-terminal GST tag)
[Phosphodiesterase 1A]
Source: Baculovirus infected Sf9 cells
Formulated in: 25 mM Tris-HCl, pH 8.0, 100 mM NaCl, 0.05% Tween-20, 50% glycerol, 20
mM glutathione, and 3 mM DTT.
Stability: >6 months at 80C
Purity: >30% by SDS-PAGE.
Specific Activity: 123 U/ug. 1 unit will lease 1 nmole phosphate per minute from 400 uM 5-AMP at 30
C in a reaction buffer of 10 mM Tris-HCl, pH 7.4, 0.2 mM MgCl2. Assay buffer: 10
mM Tris-HCl, pH 7.4, 0.2 mM MgCl2, 0.2 mM CaCl2, and 240 nM Calmodulin; 3, 5-cAMP
substrate: 0.4 mM; PDE1A: 1 ng/ul.
Application: useful for the study of enzyme kinetics, screening inhibitors, and selectivity
profiling.
Reference:
1. Nagel,D.J., Aizawa,T., Jeon,K.I., Liu,W., Mohan,A., Wei,H., Miano,J.M., Florio,V.A., Gao,P.,
Korshunov,V.A., Berk,B.C. and Yan,C. Circ. Res. 98 (6), 777-784 (2006)
2. Goraya,T.A., Masada,N., Ciruela,A. and Cooper,D.M. J. Biol. Chem. 279 (39), 40494-40504 (2004)
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PDE1B (human, recombinant, N-terminal GST tag)
Source: Baculovirus infected Sf9 cells
Formulated in: 25 mM Tris-HCl, pH 8.0, 100 mM NaCl, 0.05% Tween-20, 50% glycerol, 20
mM glutathione, and 3 mM DTT.
Stability: >6 months at 80C
Purity: >50% by SDS-PAGE.
Specific Activity: 450 U/ug. 1 unit will lease 1 pmole phosphate per minute from 0.2 mM 3,
5-cAMP at 30 C in a reaction buffer of 10 mM Tris-HCl, pH 7.4, 0.2 mM MgCl2. Assay buffer:
10 mM Tris-HCl, pH 7.4, 0.2 mM MgCl2, 0.2 mM CaCl2, and 240 nM Calmodulin; 3, 5-cAMP
substrate: 0.2 mM; PDE1B: 2 ng/ul.
Application: useful for the study of enzyme kinetics, screening inhibitors, and selectivity
profiling.
Reference:
1. Bender,A.T. and Beavo,J.A. Proc. Natl. Acad. Sci. U.S.A. 103 (2), 460-465 (2006)
2. Bender,A.T., Ostenson,C.L., Wang,E.H. and Beavo,J.A. Proc. Natl. Acad. Sci. U.S.A. 102 (2),
497-502 (2005)
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PDE1C (mouse, recombinant, N-terminal GST tag)Source: Baculovirus infected Sf9 cells
Formulated in: 25 mM Tris-HCl, pH 8.0, 100 mM NaCl, 0.05% Tween-20, 50% glycerol, 20
mM glutathione, and 3 mM DTT.
Stability: >6 months at 80C
Purity: >50% by SDS-PAGE.
Specific Activity: 18000 U/ug. 1 unit will lease 1 pmole phosphate per minute from 0.2 mM
3, 5-cAMP at 30 C in a reaction buffer of 10 mM Tris-HCl, pH 7.4, 0.2 mM MgCl2. Assay
buffer: 10 mM Tris-HCl, pH 7.4, 0.2 mM MgCl2, 0.2 mM CaCl2, and 240 nM Calmodulin; 3, 5-cAMP substrate: 0.2 mM; PDE1C: 0.5 ng/ul.
Application: useful for the study of enzyme kinetics, screening inhibitors, and selectivity
profiling.
Reference:
1. Gong,S., Zheng,C., Doughty,M.L., Losos,K., Didkovsky,N., Schambra,U.B.,
Nowak,N.J., Joyner,A., Leblanc,G., Hatten,M.E. and Heintz,N. Nature 425 (6961), 917-925 (2003)
2. Spence,S., Rena,G., Sullivan,M., Erdogan,S. and Houslay,M.D. Biochem. J. 321 (PT 1), 157-163 (1997)
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PDE3A (human, recombinant, N-terminal GST tag)Source: Baculovirus infected Sf9 cells
Formulated in: 25 mM Tris-HCl, pH 8.0, 100 mM NaCl, 0.05% Tween-20, 50% glycerol, 20
mM glutathione, and 3 mM DTT.
Stability: >6 months at 80C
Purity: >50% by SDS-PAGE.
Specific Activity: 1380 U/ug. 1 unit will lease 1 pmole phosphate per minute from 400 uM
5-AMP AT 30 C in a reaction buffer of 10 mM Tris-HCl, pH 7.4, 0.2 mM MgCl2. Assay buffer:
10 mM Tris-HCl, pH 7.4, 0.2 mM MgCl2 ; 3, 5-cAMP substrate: 0.4 mM; PDE3A: 1 ng/ul.
Application: useful for the study of enzyme kinetics, screening inhibitors, and selectivity
profiling.
Reference:
1. Hung,S.H., Zhang,W., Pixley,R.A., Jameson,B.A., Huang,Y.C., Colman,R.F. and Colman,R.W. J. Biol. Chem. 281 (39), 29236-29244 (2006)
2. Hambleton,R., Krall,J., Tikishvili,E., Honeggar,M., Ahmad,F., Manganiello,V.C. and
Movsesian,M.A. J. Biol. Chem. 280 (47), 39168-39174 (2005)
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PDE4A1A (human, recombinant, N-terminal GST tag)Source: Baculovirus infected Sf9 cells
Formulated in: 25 mM Tris-HCl, pH 8.0, 100 mM NaCl, 0.05% Tween-20, 50% glycerol, 20
mM glutathione, and 3 mM DTT.
Stability: >6 months at 80C
Purity: >50% by SDS-PAGE.
Specific Activity: 2580 U/ug. 1 unit will lease 1 pmole phosphate per minute from 400 uM
5-AMP AT 30 C in a reaction buffer of 10 mM Tris-HCl, pH 7.4, 0.2 mM MgCl2. Assay buffer:
10 mM Tris-HCl, pH 7.4, 0.2 mM MgCl2 ; 3, 5-cAMP substrate: 0.4 mM; PDE4A: 1 ng/ul.
Application: useful for the study of enzyme kinetics, screening inhibitors, and selectivity
profiling.
Reference:
1. Sullivan,M., Rena,G., Begg,F., Gordon,L., Olsen,A.S. and Houslay,M.D.
Journal Biochem. J. 333 (Pt 3), 693-703 (1998)
2. Huston E, Gall I, Houslay TM, Houslay MD. J Cell Sci. 2006 Sep 15;119(Pt
18):3799-810. (2006)
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PDE4B1 (human, recombinant, N-terminal GST tag)Source: Baculovirus infected Sf9 cells
Formulated in: 25 mM Tris-HCl, pH 8.0, 100 mM NaCl, 0.05% Tween-20, 50% glycerol, 5 mM
glutathione, and 3 mM DTT.
Stability: >6 months at 80C
Purity: >50% by SDS-PAGE.
Specific Activity: 10000 U/ug. 1 unit will lease 1 pmole phosphate per minute from 400 uM
5-GMP at 30 C in a reaction buffer of 10 mM Tris-HCl, pH 7.4, 1 mM MgCl2. Assay buffer: 10
mM Tris-HCl, pH 7.4, 1 mM MgCl2 ; 3, 5-cAMP substrate: 0.4 mM; PDE4B1: 0.2 ng/ul.
Application: useful for the study of enzyme kinetics, screening inhibitors, and selectivity
profiling.
Reference:
1. Shah,V.O., Dominic,E.A., Moseley,P., Pickett,G., Fleet,M., Ness,S. and Raj,D.S
JOURNAL Am. J. Kidney Dis. 48 (4), 616-628 (2006)
2. Smith,P.G., Wang,F., Wilkinson,K.N., Savage,K.J., Klein,U., Neuberg,D.S., Bollag,G.,
Shipp,M.A. and Aguiar,R.C.Blood 105 (1), 308-316 (2005)
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PDE5A
(bovine) (recombinant) [Phosphodiesterase
5A]
[Phosphodiesterase 5A (bovine)
(recombinant) CGB-PDE (bovine) (recombinant);
cGMP-specific
3
,5-cyclic phosphodiesterase (bovine) (recombinant)
ALX-201-257-1
1 Vial
Background/Technical
Information
Assay
for Measuring PDE5 Activity
Assay
Overview:
cGMP/[3H]-cGMP
mixture is incubated with the PDE5 preparation and the reaction is stopped.
Produced GMP/[3H]-GMP is converted into guanosine/[3H]-guanosine after the
phosphate group is removed by nucleotide phosphatase (from snake venom).
Guanosine/[3H]-guanosine mixture does not bind to DEAE Sephadex 25, while the
charged cGMP and GMP bind to the column.
Equipment
Required:
Water
bath at
30C
.
Heat
block at
100C
.
Columns
with 1.5ml bed of DEAE Sephadex 25 media: One per reaction sample. Columns
should be pre-washed with 2ml of 500mM NaCl solution, 10ml of column wash buffer
and 4ml of water. Drain the liquid before use of the column.
Scintillation
vials and counter.
Additional
Reagents Required:
Enzyme
Dilution Buffer: 25mM TEA, pH 7.5, 0.2mg/ml BSA, 15mM MgCl2 and 1mM EGTA
Assay
Buffer: 25mM TEA, pH 7.5, containing 0.2mg/ml BSA, 15mM MgCl2, 1mM EGTA, 60M
cGMP and [3H]-cGMP. Add [3H]-cGMP to 400000-600000 cpm/ml. Column
Wash
Buffer: 25mM TRIS, pH 7.5.
Nucleotidase
Reagent: Weight out several mg of snake venom from Crotalus atrox. Mark the
weigh on the tube. Keep on ice.
Scintillation
Fluid.
cGMP
Degradation Reaction:
a)
Prepare a
1:10-1:20
dilution of PDE5A (bovine) (recombinant) in enzyme dilution buffer.
b)
Preincubate 250l of assay buffer in a 1.5ml eppendorf tube at
30C
for 2-3 min.
c)
Start the reaction by adding 1l of diluted PDE5 to 250l of assay buffer.
Incubate the reaction for
2-5 min. at
30C
. Do not add PDE5 into one or
two tubes. They will be used to determine the background
(cpmbgrnd).
d)
To stop the reaction, transfer the assay tube to
100C
heating block. Incubate for
5 min. and transfer on ice. (Optional: centrifuge the sample for 5 min. at
14000 g to precipitate the denatured protein). The sample can be stored at
this time before further processing.
e)
Dilute the snake venom to 10mg/ml in 25mM TEA, pH 7.5. Add 10ml of venom
solution to the chilled reaction sample and transfer to
30C
. Incubate for 10-15 min. and
then transfer on ice.
Guanosine
Quantification:
f)
Add 7ml of scintillation fluid to a scintillation vial and place under the
column prepared as described above.
g)
Transfer the reaction sample (260l) onto the column. Wait 1-2 min. for the
sample to completely penetrate into the column and wash the column by loading
4ml of distilled water. Collect the eluted [3H]-guanosine in the scintillation
vial.
h)
Shake the vial to mix the liquids and proceed to measure the amount of eluted
radioactivity.
i)
Determine the amount of degraded cGMP by using the following formula: cGMP= (cpmsample - cpmbgrnd)/cpmtotal
x 15nmoles
j)
The column can be regenerated by the wash cycles described above (see equipment
needed).
Figure 1: Activity of PDE5A (bovine) (recombinant) (Prod. No. ALX-201-257).
Method: The cGMP-degrading activity of 0.1μl of PDE5A (bovine) (recombinant) was measured in 250μl reaction buffer with 60μM cGMP. Reaction was stopped at 2, 3 and 5 min. and processed as described in the assay
protocol.
Figure 2: Purity and quantitation of PDE5A (bovine) (recombinant) (Prod. No. ALX-201-257).
Method: Lane 1) Western blot of the PDE5A PDE5A (bovine) (recombinant) using PAb to PDE5A (Prod. No. ALX-210-099). Lanes 3 to 6) Coomassie staining of 10, 5, 2.5, 1.25μl of PDE5A preparation. Lane 7)
Molecular weight marker top to bottom: 220, 128, 82, 43, 32kDa. Lanes 8 to 11) Coomassie staining of 2, 1, 0.5, 0.25μg of BSA. Asterics indicates PDE5A. Intensity of staining in lane 6 (1.25μl PDE5A) is similar to the intensity of staining in lane 10 (0.5μg BSA), and the intensity in lane 5 (2.5μl PDE5A) is similar to the staining in lane 9 (1μg protein), thus the PDE5A concentration in the preparation is ~0.4mg/ml.
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PDE5A1 (human, recombinant, N-terminal GST tag)Source: Baculovirus infected Sf9 cells
Formulated in: 25 mM Tris-HCl, pH 8.0, 100 mM NaCl, 0.05% Tween-20, 50% glycerol, 5 mM
glutathione, and 3 mM DTT.
Stability: >6 months at 80C
Purity: >40% by SDS-PAGE.
Specific Activity: 1300 U/ug. 1 unit will lease 1 pmole phosphate per minute from 400 uM
5-GMP at 30 C in a reaction buffer of 10 mM Tris-HCl, pH 7.4, 1 mM MgCl2. Assay buffer: 10
mM Tris-HCl, pH 7.4, 1 mM MgCl2 ; 3, 5-cGMP substrate: 0.4 mM; PDE5A1: 0.2 ng/ul.
Application: useful for the study of enzyme kinetics, screening inhibitors, and selectivity
profiling.
Reference:
1. Filippi,S., Morelli,A., Sandner,P., Fibbi,B., Mancina,R., Marini,M., Gacci,M.,
Vignozzi,L., Vannelli,G.B., Carini,M., Forti,G. and Maggi,M. Endocrinology 148 (3),
1019-1029 (2007)
2. Bruder,S., Schultz,A. and Schultz,J.E. J. Biol. Chem. 281 (29), 19969-19976 (2006)
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PDE7A human, recombinant, N-terminal GST tag
[Phosphodiesterase 7A]
Specific Activity: 302 pmol/min/μg.
Assay conditions: 10 mM Tris-HCl, pH7.4, 10 mM MgCl2, 1 mM MnCl2, 400 μM
cAMP, 2.5 kU 5' nucleotidase, 37C, 20min.
Application: Useful for the study of enzyme kinetics, screening inhibitors, and selectivity
profiling.
Quality Assurance
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PDE7B human, recombinant, N-terminal GST tag
[Phosphodiesterase 7B]
Specific Activity: 53 pmol/min/μg.
Assay conditions: 10 mM Tris-HCl, pH7.4, 10 mM MgCl2, 1 mM MnCl2, 400 μM
cAMP, 2.5 kU 5' nucleotidase, 37C, 20min.
Application: Useful for the study of enzyme kinetics, screening inhibitors, and selectivity
profiling.
Formulated in: 25 mM Tris-HCl, pH 8.0, 100 mM NaCl, 0.05% Tween-20, 50% glycerol, and
3 mM DTT.
Stability: >6 months at 80C
References:
1. Gardner,C., et al., Biochem. Biophys. Res. Commun. 272 (1), 186-192 (2000)
2. Sasaki,T., et al., Biochem. Biophys. Res. Commun. 271 (3), 575-583 (2000)
Quality Assurance 
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PDE8A1 (human, recombinant, N-terminal GST tag)Source: Baculovirus infected Sf9 cells
Formulated in: 25 mM Tris-HCl, pH 8.0, 100 mM NaCl, 0.05% Tween-20, 30% glycerol, 5 mM
glutathione, and 3 mM DTT.
Stability: >6 months at 80C
Purity: >40% by SDS-PAGE.
Specific Activity: 270 U/ug. 1 unit will lease 1 pmole phosphate per minute from 400 uM 5-AMP AT 30
C in a reaction buffer of 10 mM Tris-HCl, pH 7.4, 0.2 mM MgCl2. Assay buffer: 10
mM Tris-HCl, pH 7.4, 0.2 mM MgCl2 ; 3, 5-cAMP substrate: 0.4 mM; PDE8A: 2 ng/ul.
Application: useful for the study of enzyme kinetics, screening inhibitors, and selectivity
profiling.
Reference:
1. Wu,P. and Wang,P. Proc. Natl. Acad. Sci. U.S.A. 101 (51), 17634-17639 (2004)
2. Gamanuma,M., Yuasa,K., Sasaki,T., Sakurai,N., Kotera,J. and Omori,K. Cell. Signal. 15 (6),
565-574 (2003)
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PDE9A2 (human, recombinant, N-terminal GST tag)Source: Baculovirus infected Sf9 cells
Formulated in: 25 mM Tris-HCl, pH 8.0, 100 mM NaCl, 0.05% Tween-20, 30% glycerol, 5 mM
glutathione, and 3 mM DTT.
Stability: >6 months at 80C
Purity: >75% by SDS-PAGE.
Specific Activity: 97 U/ug. 1 unit will lease 1 pmole phosphate per minute from 400 uM 5-GMP at 30
C in a reaction buffer of 10 mM Tris-HCl, pH 7.4, 1 mM MgCl2. Assay buffer: 10
mM Tris-HCl, pH 7.4, 1 mM MgCl2 ; 3, 5-cGMP substrate: 0.4 mM; PDE9A: 5 ng/ul.
Application: useful for the study of enzyme kinetics, screening inhibitors, and selectivity
profiling.
Reference:
1. Rentero,C. and Puigdomenech,P BMC Mol. Biol. 7, 39 (2006)
2. Huai,Q., Wang,H., Zhang,W., Colman,R.W., Robinson,H. and Ke,H. JOURNAL Proc. Natl. Acad. Sci. U.S.A. 101 (26), 9624-9629 (2004)
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PDE10A (human, recombinant, N-terminal GST tag)Source: Baculovirus infected Sf9 cells
Formulated in: 25 mM Tris-HCl, pH 8.0, 100 mM NaCl, 0.05% Tween-20, 50% glycerol, 20
mM glutathione, and 3 mM DTT.
Stability: >6 months at 80C
Purity: >50% by SDS-PAGE.
Specific Activity: 1280 U/ug. 1 unit will lease 1 pmole phosphate per minute from 400 uM
5-AMP AT 30 C in a reaction buffer of 10 mM Tris-HCl, pH 7.4, 0.2 mM MgCl2. Assay buffer:
10 mM Tris-HCl, pH 7.4, 0.2 mM MgCl2 ; 3, 5-cAMP substrate: 0.4 mM; PDE10A: 1 ng/ul.
Application: useful for the study of enzyme kinetics, screening inhibitors, and selectivity
profiling.
Reference:
1. Gross-Langenhoff,M., Hofbauer,K., Weber,J., Schultz,A. and Schultz,J.E. JOURNAL
J. Biol. Chem. 281 (5), 2841-2846 (2006)
2. Frame,M., Wan,K.F., Tate,R., Vandenabeele,P. and Pyne,N.J. Cell. Signal. 13 (10), 735-741 (2001)
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PDE11A4 (human, recombinant, N-terminal GST tag)
[Phosphodiesterase 11A4]
Source: Baculovirus infected Sf9 cells
Formulated in: 25 mM Tris-HCl, pH 8.0, 100 mM NaCl, 0.05% Tween-20, 50% glycerol, 5 mM
glutathione, and 3 mM DTT.
Stability: >6 months at 80C
Purity: >80% by SDS-PAGE.
Specific Activity: 2008 U/ug. 1 unit will lease 1 pmole phosphate per minute from 400 uM
5-AMP AT 30 C in a reaction buffer of 10 mM Tris-HCl, pH 7.4, 1.0 mM MgCl2. Assay buffer:
10 mM Tris-HCl, pH 7.4, 1.0 mM MgCl2 ; 3, 5-cGMP substrate: 0.4 mM; PDE11A4: 1 ng/ul.
Application: useful for the study of enzyme kinetics, screening inhibitors, and selectivity
profiling.
Reference:
1. Loughney K, Taylor J, and Florio VA Int J Impot Res. 2005, 17(4):320-5
2. Weeks JL, Zoraghi R, Beasley A, Sekhar KR, Francis SH, Corbin JD. Int J Impot
Res. 2005 Jan-Feb;17(1):5-9
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Antibodies
to PDEs (Phosphodiesterases] |
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Polyclonal
Antibody to PDE5A [Phosphodiesterase
5A; 3,5-cyclic phosphodiesterase; CGB-PDE]
ALX-210-099-C050
50 g
SPECIFICITY:
Recognizes mouse and bovine PDE5A.
APPLICATION:
Western Blot (1:10'000).
Figure 1: Western blot using PAb to PDE5A (Prod. No. ALX-210-099) at 1:1'000
dilution. Lane 1) 100μg of PDE5A-deficient SKN-BE2 neuroblastoma lysate. Lane 2) 100μg lysate mixed with 5ng of purified recombinant bovine PDE5A (Prod. No. ALX-201-257). Lane 3) 3ng of partially purified recombinant bovine PDE5A. Signal was developed for 5 sec. using ECL-Plus reagent (Amersham).
Figure 2: Western blot using PAb to PDE5A (Prod. No. ALX-210-099) at 1:1'000
dilution. Lane 1) 200μg of 15'000 x g supernatant of lysate from mouse brain. Lane 2) Mouse heart. Lane 3)
Mouse lung. Lane 4) Mouse liver. Lane 5) 5ng of purified bovine PDE5.
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Polyclonal
Antibody to PDE6α
[Phosphodiesterase
α]
ABR-PA1-720-C100
100 g
SPECIFICITY: Recognizes sheep and bovine PDE6.
APPLICATION: Western blot (1-2μg/ml).
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Polyclonal
Antibody to PDE6α'
(sheep)
[Phosphodiesterase
α]
ABR-PA1-721-R100
100 l
SPECIFICITY:
Recognizes sheep PDE6 alpha.
APPLICATION:
Western blot (1:500).
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Polyclonal
Antibody to PDE6β (mouse)
[Phosphodiesterase
β]
ABR-PA1-722-C100
100 g
SPECIFICITY:
Recognizes mouse PDE6 beta.
APPLICATION:
Immunohistochemistry, Western blot (2μg/ml).
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Polyclonal
Antibody to PDE6γ
[Phosphodiesterase
γ
]
ABR-PA1-723-R100
100 l
SPECIFICITY:
Recognizes sheep and bovine PDE6 gamma.
APPLICATION:
Western blot (1:500).
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Polyclonal
Antibody to PDE6δ
[Phosphodiesterase
δ]
ABR-PA1-726-C100
100 g
SPECIFICITY:
Recognizes bovine PDE6 delta.
APPLICATION:
Immunohistochemistry (Frozen section 1μg/ml), Western blot (1μg/ml).
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Phosphodiesteres
Inhibitors and related compounds |
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2'-O-(N'-Methylanthraniloyl)adenosine-3',5'-cyclic
monophosphate . sodium salt
[Mant-cAMP . Na]
BLG-M008-10
10 mol
BLG-M008-50
5x10 mol
Fluorescent,
membrane-permeant cyclic AMP analogue, suitable for phosphodiesterase studies.
The
compound shows a decrease in fluorescence when cleaved by PDE.
Product
Specific Literature References
New
fluorescent analogs of cAMP and cGMP available as substrates for cyclic
nucleotide phosphodiesterase: T. Hiratsuka; J. Biol. Chem. 257, 13354 (1982);
Dynamic
interaction of cAMP with the Rap guanine-nucleotide exchange factor Epac1: A.
Kraemer, et al.; J. Mol. Biol. 306, 1167 (2001)
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2'-O-(N'-Methylanthraniloyl)guanosine-3',5'-cyclic
monophosphate . sodium salt
[Mant-cGMP.Na]
BLG-M009-10
10 mol
BLG-M009-50
5x10 mol
Fluorescent,
membrane permeant cyclic GMP analogue, suitable for phosphodiesterase studies.
The compound shows a decrease in fluorescence when cleaved by PDE.
Product
Specific Literature References
New
fluorescent analogs of cAMP and cGMP available as substrates for cyclic
nucleotide phosphodiesterase: T. Hiratsuka; J. Biol. Chem. 257, 13354 (1982);
A
continuous fluorescence assay for cyclic nucleotide phosphodiesterase hydrolysis
of cyclic GMP: J.D. Johnson, et al.; Anal. Biochem. 162, 291 (1987)
Ca2+
induces an increase in cGMP-phosphodiesterase activity in squid retinal
photoreceptors: J.E. Brown & E.S. Kelman; BBRC 224, 684 (1996)
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BAY
60-7550 [2-(3,4-Dimethoxybenzyl)-7-[(1R)-1-[(1R)-1-hydroxyethyl]-4-phenylbutyl]-5-methylimidazo[5,1-f][1,2,4]triazin-4(3H)-one]
ALX-270-421-M005
5 mg
ALX-270-421-M025
25 mg
Inhibitor
of human phosphodiesterase 2 (PDE2) (IC50=5nM). Selective (>50-fold) versus
other human PDEs tested (
1C
,3A, 4B, 5A, 6, 7B, 8A, 9A,
10A, 11A) and does not affect adenosine deaminase. Raises cGMP levels in cell
culture, particularly in combination with a suitable activator of soluble
guanylyl cyclase (sGC). Raises cAMP in combination with forskolin (Prod. No.
ALX-350-001). Increases memory performance in rodents in vivo.
Product
Specific Literature References
Inhibition
of phosphodiesterase 2 increases neuronal cGMP, synaptic plasticity and memory
performance: F.G. Boess, et al.; Neuropharmacology 47, 1081 (2004)
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Cilostamide
[N-Cyclohexyl-N-methyl-4-(1,2-dihydro-2-oxo-6-quinolyloxy)butyramide
;
OCP
3689]
ALX-270-404-M005
5 mg
ALX-270-404-M025
25 mg
Selective
inhibitor (IC50=70nM) of phosphodiesterase 3 (PDE3). Reverses the established
effects of leptin on food intake and body weight. Blocks the leptin-induced
tyrosine phosphorylation of STAT3 at the hypothalamic level.
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Forskolin
ALX-350-001-M001
1 mg
ALX-350-001-M005
5 mg
ALX-350-001-M010
10 mg
ALX-350-001-M025
25 mg
ALX-350-001-M050
50 mg
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IBMX
[3-Isobutyl-1-methylxanthine]
ALX-480-038-G001
1 g
ALX-480-038-M500
500 mg
Potent,
non-specific inhibitor of phosphodiesterases. More potent than theophylline (Prod.
No. ALX-480-062) at adenosine receptors. Accelerates conversion of mouse
fibroblast cells into adipose cells.
Product
Specific Literature References
Effects
of xanthine derivatives on lipolysis and on adenosine 3',5'- monophosphate
phosphodiesterase activity: J.A. Beavo, et al.; Mol. Pharmacol. 6, 597 (1970)
Adenosine
3':5'-cyclic monophosphate and insulin release: W. Montague & J.R. Cook;
Biochem. J. 120, 9P (1970)
The
role of adenosine 3':5'-cyclic monophosphate in the regulation of insulin
release by isolated rat islets of Langerhans: W. Montague & J.R. Cook;
Biochem. J. 122, 115 (1971)
Cyclic
nucleotide phosphodiesterase activity in normal mouse pancreatic islets: S.J.
Ashcroft, et al.; FEBS Lett. 20, 263 (1972)
The
mode of action of adenosine 3:5-cyclic monophosphate in mammalian islets
of Langerhans. Effects of insulin secretagogues on islet-cell protein kinase
activity: W. Montague & S.L. Howell; Biochem. J. 134, 321 (1973)
Effects
of methylxanthines on adenosine
3
,5-monophosphate and
corticosterone in the rat adrenal: A. Peytremann, et al.; Endocrinology 92, 525
(1973)
Concentration
of adenosine 3:5-cyclic monophosphate in mouse pancreatic islets measured
by a protein-binding radioassay: R.H. Cooper, et al.; Biochem. J. 134, 599
(1973)
Determination
of theophylline in plasma by electron capture gas chromatography: H.A.
Schwertner, et al.; Anal. Chem. 48, 1875 (1976)
Methyl
xanthine phosphodiesterase inhibitors behave as prostaglandin antagonists in a
perfused rat mesenteric artery preparation: D.F. Horrobin, et al.;
Prostaglandins 13, 33 (1977)
Selective
inhibition of cyclic nucleotide phosphodiesterases by analogues of
1-methyl-3-isobutylxanthine: G.L. Kramer, et al.; Biochemistry 16, 3316 (1977)
Cyclic
nucleotide phosphodiesterases of human and rat gastric mucosa: U. Klotz, et al.;
Naunyn-Schmiedebergs Arch. Pharmacol. 296, 187 (1977)
Allergic
reactions, cyclic AMP and histamine release: P.S. Skov, et al.; Experientia 33,
965 (1977)
Differentiation
of 3T3-L2 fibroblasts into adipose cells in bromodeoxyuridine-suppressed
cultures: T.R. Russell; PNAS 76, 4451 (1979)
Inhibition
of growth of primary and metastatic Lewis lung carcinoma cells by the
phosphodiesterase inhibitor isobutylmethylxanthine: P. Janik, et al.; Cancer
Res. 40, 1950 (1980)
Induction
of a transient elevation in intracellular levels of adenosine-
3
,5-cyclic monophosphate by
chemotactic factors: an early event in human neutrophil activation: L.
Simchowitz, et al.; J. Immunol. 124, 1482 (1980)
Selective
inhibition of cyclic AMP and cyclic GMP phosphodiesterases of cardiac nuclear
fraction: G.S. Ahluwalia & A.R. Rhoads; Biochem. Pharmacol. 31, 665 (1982)
Characterization
of the A2 adenosine receptor labeled by [3H]NECA in rat striatal membranes: R.F.
Bruns, et al.; Mol. Pharmacol. 29, 331 (1986)
Methylxanthine
inhibitors of phosphodiesterases: J.N. Wells & J.R. Miller; Methods Enzymol.
159, 489 (1988)
Psychomotor-stimulant
effects of 3-isobutyl-1-methylxanthine: comparison with caffeine and
7-(2-chloroethyl) theophylline: V.L. Coffin and R.D. Spealman; Eur. J. Pharmacol.
170, 35 (1989)
Differential
effects of Ro 20-1724 and isobutylmethylxanthine on the basal force of
contraction and beta-adrenoceptor-mediated response in the rat ventricular
myocardium: Y. Katano & M. Endoh; BBRC 167, 123 (1990)
Bemoradan--a
novel inhibitor of the rolipram-insensitive cyclic AMP phosphodiesterase from
canine heart tissue: J.B. Moore, Jr., et al.; Biochem. Pharmacol. 42, 679 (1991)
Effect
of an antihypertensive hydrazine derivative on Ca2+ current of single frog
cardiac cells: F. Scamps, et al.; Eur. J. Pharmacol. 244, 119 (1993)
Isobutylmethylxanthine
and other classical cyclic nucleotide phosphodiesterase inhibitors affect
cAMP-dependent protein kinase activity: C. Tomes, et al.; Cell. Signal. 5, 615
(1993)
|
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Milrinone
[1,6-Dihydro-2-methyl-6-oxo-3,4'-bipyridine-5-carbonitrile]
ALX-270-083-M005
5 mg
Selective
inhibitor of phosphodiesterase 3 (PDE3).
Product
Specific Literature References
Isolation
and characterization of bovine cardiac muscle cGMP-inhibited phosphodiesterase:
a receptor for new cardiotonic drugs: S.A. Harrison, et al.; Mol. Pharmacol. 29,
506 (1986)
Effects
of selective inhibitors on cyclic nucleotide phosphodiesterases of rabbit aorta:
H.S. Ahn, et al.; Biochem. Pharmacol. 38, 3331 (1989)
Effects
of isozyme-selective phosphodiesterase inhibitors on rat aorta and human
platelets: smooth muscle tone, platelet aggregation and cAMP levels: S.H.
Lindgren, et al.; Acta Physiol. Scand. 140, 209 (1990)
Bemoradan--a
novel inhibitor of the rolipram-insensitive cyclic AMP phosphodiesterase from
canine heart tissue: J.B. Moore, Jr., et al.; Biochem. Pharmacol. 42, 679 (1991)
In
vitro pharmacology of R
80122, a
novel phosphodiesterase
inhibitor: D. Wilhelm, et al.; J. Cardiovasc. Pharmacol. 20, 705 (1992)
Pharmacokinetics
of intravenous milrinone in patients undergoing cardiac surgery: J.M. Bailey, et
al.; Anesthesiology 81, 616 (1994)
|
|
MY-5445
[1-(3-Chlorophenylamino)-4-phenylphthalazine]
ALX-270-085-M001
1 mg
ALX-270-085-M005
5 mg 9
Selective
inhibitor of phosphodiesterase 5 (PDE5).
Product
Specific Literature References
Effect
of 1-(3-chloroanilino)-4-phenylphthalazine (MY-5445), a specific inhibitor of
cyclic GMP phosphodiesterase, on human platelet aggregation: M. Hagiwara, et al.;
J. Pharmacol. Exp. Ther. 228, 467 (1984)
Peripheral
analgesia and activation of the nitric oxide-cyclic GMP pathway: I.D. Durate, et
al.; Eur. J. Pharmacol. 186, 289 (1990)
Inhibitory
effects of natriuretic peptides on vasopressin neurons mediated through cGMP and
cGMP-dependent protein kinase in vitro:
N. Akamatsu
, et al.; J. Neuroendocrinol.
5, 517 (1993)
cAMP
modulates cGMP-mediated cerebral arteriolar relaxation in vivo: H.L. Xu, et al.;
Am. J. Physiol. Heart Circ. Physiol. 287, H2501 (2004);
|
|
Rolipram
[4-[3-(Cyclopentyloxy)-4-methoxyphenyl]-2-pyrrolidinone]
ALX-270-119-M005
5 mg
ALX-270-119-M025
25 mg
Selective
inhibitor of phosphodiesterase 4 (PDE4).
Product
Specific Literature References
Stereospecific
binding of the antidepressant rolipram to brain protein structures: H.H.
Schneider, et al.; Eur. J. Pharmacol. 127, 105 (1986)
The
identification of a new cyclic nucleotide phosphodiesterase activity in human
and guinea-pig cardiac ventricle. Implications for the mechanism of action of
selective phosphodiesterase inhibitors: M.L. Reeves, et al.; Biochem. J. 241,
535 (1987)
Bemoradan--a
novel inhibitor of the rolipram-insensitive cyclic AMP phosphodiesterase from
canine heart tissue: J.B. Moore, et al.; Biochem. Pharmacol. 42, 679 (1991)
Comparison
of phosphodiesterase III, IV and dual III/IV inhibitors on bronchospasm and
pulmonary eosinophil influx in guinea pigs: D.C. Underwood, et al.; J. Pharmacol.
Exp. Ther. 270, 250 (1994)
|
|
Trequinsin
. hydrochloride [9,10-Dimethoxy-2-mesitylimino-3-methyl-2,3,6,7-tetrahydro-4H-pyrimido-[6,1a]-isoquinolin-4-one.HCl
;
HL
725.HCl]
ALX-270-126-M010
10 mg
Ultrapotent,
highly selective inhibitor of cGMP-inhibited phosphodiesterase (PDE lll) in
vitro. Potentiates adenosine-stimulated cAMP accumulation.
Product
Specific Literature References
HL
725, an extremely potent inhibitor of platelet phosphodiesterase and induced
platelet aggregation in vitro: D. Rupert & K.U. Weithmann; Life Sci. 31,
2037 (1982)
Arachidonic
acid metabolites, ADP and thrombin modulate occlusive thrombus formation over
extensive arterial injury in the rat: F. DeClerck, et al.; Blood Coag. Fibrinol.
1, 247 (1990)
Heparin-binding
growth factor-1 modulation of plasminogen activator inhibitor-1 expression.
Interaction with cAMP and protein kinase C- mediated pathways: B.A. Konkle, et
al.; J. Biol. Chem. 265, 21867 (1990);
Phosphodiesterase
II, the cGMP-activatable cyclic nucleotide phosphodiesterase, regulates cyclic
AMP metabolism in PC12 cells: M.E. Whalin, et al.; Mol. Pharmacol. 39, 711
(1991)
|
|
Vinpocetine
[Eburnamenine-14-carboxylic acid-ethyl ester]
ALX-270-150-M005
5 mg
ALX-270-150-M025
25 mg
Selective
inhibitor of Ca2+/calmodulin-dependent phosphodiesterase 1 (PDE1).
Product
Specific Literature References
Effects
of vinpocetine on cyclic nucleotide metabolism in vascular smooth muscle: M.
Hagiwara, et al.; Biochem. Pharmacol. 33, 453 (1984)
Effects
of selective inhibitors on cyclic nucleotide phosphodiesterases of rabbit aorta:
H.S. Ahn, et al.; Biochem. Pharmacol. 38, 3331 (1989)
Regulation
of cyclic AMP metabolism in bovine adrenal medullary cells: P.D. Marley &
K.A. Thomsom; Biochem. Pharmacol. 44, 2105 (1992)
Cyclic
3',5'-nucleotide diesterases in dynamics of cAMP and cGMP in rat collecting duct
cells: M. Yamaki, et al.; Am. J. Physiol. 262, F957 (1992)
Modulation
of TNF alpha and IL-1 beta from endotoxin-stimulated monocytes by selective PDE
isozyme inhibitors: K. Molnar-Kimber, et al.; Agents Actions 39, C77 (1993)
|
|
W-5
. hydrochloride
[N-(6-Aminohexyl)-1-naphthalenesulfonamide . HCl]
ALX-270-151-M005
5 mg
ALX-270-151-M025
25 mg
Antagonist
of calmodulin, inhibiting Ca2+/calmodulin-regulated phosphodiesterase (PDE I)
and myosin light chain kinase.
Product
Specific Literature References
Hydrophobic
regions function in calmodulin-enzyme(s) interactions: T. Tanaka & H. Hidaka;
J. Biol. Chem. 255, 11078 (1980);
N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide,
a calmodulin antagonist, inhibits cell proliferation: H. Hidaka, et al.; PNAS
78, 4354 (1981)
[Pharmacology
of calmodulin: calmodulin antagonist (author's transl)]: H. Hidaka; Prot. Nucl.
Acid Enz. 26, 977 (1981)
|
|
W-7
. hydrochloride
[N-(6-Aminohexyl)-5-chloro-1-naphthalenesulfonamide . HCl]
ALX-270-153-M005
5 mg
ALX-270-153-M025
25 mg
Antagonist
of calmodulin, inhibiting activation of Ca2+/calmodulin-regulated
phosphodiesterase (PDE I) and myosin light chain kinase.
Product
Specific Literature References
N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide,
a calmodulin antagonist, inhibits cell proliferation: H. Hidaka, et al.; PNAS
78, 4354 (1981)
Activity-structure
relationship of calmodulin antagonists, Naphthalenesulfonamide derivatives: H.
Hidaka, et al.; Mol. Pharmacol. 20, 571 (1981)
Calmodulin
antagonists enhance calcium binding to calmodulin: M. Inagaki, et al.;
Pharmacology 27, 125 (1983)
Direct
interaction of calmodulin antagonists with Ca2+/calmodulin- dependent cyclic
nucleotide phosphodiesterase: H. Itoh & H. Hidaka; J. Biochem. 96, 1721
(1984)
|
|
W-12
. hydrochloride
[N-(4-Aminobutyl)-2-naphthalenesulfonamide . HCl]
ALX-270-155-M005
5 mg
ALX-270-155-M025
25 mg
Antagonist
of calmodulin, inhibiting activation of Ca2+/calmodulin-dependent
phosphodiesterase (PDE I) and myosin light chain kinase.
Product
Specific Literature References
T.
Tanaka and H. Hidaka; J. Biol. Chem. 255, 11078 (1980);
[Pharmacology
of calmodulin: calmodulin antagonist (author's transl)]: H. Hidaka; Prot. Nucl.
Acid Enz. 26, 977 (1981)
N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide,
a calmodulin antagonist, inhibits cell proliferation: H. Hidaka, et al.; PNAS
78, 4354 (1981)
|
|
W-13
. hydrochloride
[N-(4-Aminobutyl)-5-chloro-2-naphthalenesulfonamide . HCl]
ALX-270-156-M005
5 mg
ALX-270-156-M025
25 mg
Antagonist
of calmodulin, inhibiting activation of Ca2+/calmodulin-dependent
phosphodiesterase (PDE I) and myosin light chain kinase.
Product
Specific Literature References
Hydrophobic
regions function in calmodulin-enzyme(s) interactions: T. Tanaka & H. Hidaka;
J. Biol. Chem. 255, 11078 (1980);
[Pharmacology
of calmodulin: calmodulin antagonist (author's transl)]: H. Hidaka; Prot. Nucl.
Acid Enz. 26, 977 (1981)
Activity-structure
relationship of calmodulin antagonists, Naphthalenesulfonamide derivatives: H.
Hidaka, et al.; Mol. Pharmacol. 20, 571 (1981)
Naphthalenesulfonamides
as calmodulin antagonists: H. Hidaka & T. Tanaka; Meth. Enzymol. 102, 185
(1983)
Calmodulin
antagonists enhance calcium binding to calmodulin: M. Inagaki, et al.;
Pharmacology 27, 125 (1983)
Direct
interaction of calmodulin antagonists with Ca2+/calmodulin- dependent cyclic
nucleotide phosphodiesterase: H. Itoh & H. Hidaka; J. Biochem. 96, 1721
(1984)
Tamoxifen-resistant
human breast cancer cell growth: inhibition by thioridazine, pimozide and the
calmodulin antagonist, W-13: J.S. Stroble & V.A. Peterson; J. Pharm. Exp.
Ther. 263, 186 (1992)
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|
Zaprinast
[1,4-Dihydro-5-[2-propoxyphenyl]-7H-1,2,3-triazolo[4,5-d]pyrimidine-7-one
,
M&B
22,948]
ALX-430-020-M010
10 mg
ALX-430-020-M050
50 mg
Phosphodiesterase
(PDE) inhibitor.
Product
Specific Literature References
Inhibition
and stimulation of photoreceptor phosphodiesterases by dipyridamole and M&B
22,948: P.G. Gillespie and J.A. Beavo; Mol. Pharmacol. 36, 773 (1989)
Primary
sequence of cyclic nucleotide phosphodiesterase isozymes and the design of
selective inhibitors: J.A. Beavo & D.H. Reifsnyder; TIPS 11, 150 (1990)
The
catalytic subunit of protein kinase A triggers activation of the type V cyclic
GMP-specific phosphodiesterase from guinea-pig lung: F. Burns, et al.; Biochem.
J. 283, 487 (1992)
Cyclic
nucleotide phosphodiesterases from frog atrial fibers: isolation and drug
sensitivities: C. Lugnier, et al.; Am. J. Physiol. 262, H654 (1992)
Zaprinast
increases cyclic GMP levels in plasma and in aortic tissue of rats: R.L. Dundore,
et al.; Eur. J. Pharmacol. 249, 293 (1993)
Reversal
of nitroglycerin tolerance in vitro by the cGMP- phosphodiesterase inhibitor
zaprinast: E.D. Pagani, et al.; Eur. J. Pharmacol. 243, 141 (1993)
The
nitric oxide--cyclic GMP pathway and synaptic depression in rat hippocampal
slices: C.L. Boulton, et al.; Eur. J. Neurosci. 6, 1528 (1994)
The
PDE inhibitor zaprinast enhances NO-mediated protection against vascular leakage
in reperfused lungs: H. Schutte, et al.; Am. J. Physiol. Lung Cell Mol. Physiol.
279, L496 (2000);
Phosphodiesterase
5 inhibitor, zaprinast, selectively increases cerebral blood flow in the
ischemic penumbra in the rat brain: F. Gao, et al.; Neurol. Res. 27, 638 (2005)
Zaprinast,
a well-known cyclic guanosine monophosphate-specific phosphodiesterase inhibitor,
is an agonist for GPR35: Y. Taniguchi, et al.; FEBS Lett. 580, 5003 (2006)
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