phosphodiesterase 5A

Target id: 1304

Nomenclature: phosphodiesterase 5A

Abbreviated Name: PDE5A

Family: Phosphodiesterases, 3',5'-cyclic nucleotide (PDEs)

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

   GtoImmuPdb view: OFF :     phosphodiesterase 5A has curated GtoImmuPdb data

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 875 4q27 PDE5A phosphodiesterase 5A
Mouse - 865 3 53.69 cM Pde5a phosphodiesterase 5A, cGMP-specific
Rat - 833 2q42 Pde5a phosphodiesterase 5A
Previous and Unofficial Names
cGMP-binding cGMP specific phosphodiesterase 5A2 | PDE5A2 | PDE5A1 | phosphodiesterase 5A, cGMP-specific
Database Links
BRENDA
CATH/Gene3D
DrugBank Target
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
SynPHARM
UniProtKB
Wikipedia
Enzyme Reaction
EC Number: 3.1.4.17
Activators (Human)
Protein kinase A, protein kinase G  [5]
Rank order of affinity (Human)
cyclic GMP > cyclic AMP

Download all structure-activity data for this target as a CSV file

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
compound 53 [PMID: 19631533] Hs Inhibition 10.3 pIC50 6
pIC50 10.3 (IC50 5x10-11 M) [6]
vardenafil Hs Inhibition 9.7 pIC50 3
pIC50 9.7 (IC50 2x10-10 M) [3]
T0156 Hs Inhibition 9.5 pIC50 7
pIC50 9.5 (IC50 3.16x10-10 M) [7]
PF-00489791 Hs Inhibition 9.1 pIC50 4
pIC50 9.1 (IC50 7.1x10-10 M) [4]
gisadenafil Hs Inhibition 8.9 pIC50 9
pIC50 8.9 [9]
sildenafil Hs Inhibition 8.4 – 9.0 pIC50 10,13
pIC50 8.4 – 9.0 (IC50 3.9x10-9 – 1x10-9 M) [10,13]
tadalafil Hs Inhibition 8.5 pIC50 8
pIC50 8.5 (IC50 3x10-9 M) [8]
milrinone Hs Inhibition 7.3 pIC50
pIC50 7.3 (IC50 4.91x10-8 M)
SCH51866 Hs Inhibition 7.2 pIC50 11
pIC50 7.2 (IC50 6.31x10-8 M) [11]
zaprinast Hs Inhibition 6.8 pIC50 10
pIC50 6.8 (IC50 1.58x10-7 M) [10]
ibudilast Hs Inhibition 4.0 pIC50 2
pIC50 4.0 (IC50 1.03x10-4 M) [2]
nitrosoprodenafil Hs Inhibition - - 12
[12]
Inhibitor Comments
Tadalafil is selective for PDE5A over other PDEs tested [8]. Vardenafil is also selective for PDE5A, the next closest inhibitory effect is on PDE3 (IC50 1nM) [3].
Immunopharmacology Comments
The role of PDE5A in immuno-oncology is reviewed in [1].
Immuno Process Associations
Immuno Process:  T cell (activation)
Immuno Process ID:  4
Comment: 
GO Annotation:  Associated to GO processes, IEA only
GO Processes:  negative regulation of T cell proliferation (GO:0042130) IEA
References: 
Immuno Process:  Immune regulation
Immuno Process ID:  6
Comment: 
GO Annotation:  Associated to GO processes, IEA only
GO Processes:  negative regulation of T cell proliferation (GO:0042130) IEA
References: 
Immuno Process:  Chemotaxis & migration
Immuno Process ID:  10
Comment: 
GO Annotation:  Associated to GO processes, IEA only
GO Processes:  negative regulation of T cell proliferation (GO:0042130) IEA
References: 
Immuno Process:  Cellular signalling
Immuno Process ID:  11
Comment: 
GO Annotation:  Associated to GO processes, IEA only
GO Processes:  negative regulation of T cell proliferation (GO:0042130) IEA
References: 

References

Show »

1. Adams JL, Smothers J, Srinivasan R, Hoos A. (2015) Big opportunities for small molecules in immuno-oncology. Nat Rev Drug Discov14 (9): 603-22. [PMID:26228631]

2. Allcock RW, Blakli H, Jiang Z, Johnston KA, Morgan KM, Rosair GM, Iwase K, Kohno Y, Adams DR. (2011) Phosphodiesterase inhibitors. Part 1: Synthesis and structure-activity relationships of pyrazolopyridine-pyridazinone PDE inhibitors developed from ibudilast. Bioorg. Med. Chem. Lett.21 (11): 3307-12. [PMID:21530250]

3. Boyle CD, Xu R, Asberom T, Chackalamannil S, Clader JW, Greenlee WJ, Guzik H, Hu Y, Hu Z, Lankin CM et al.. (2005) Optimization of purine based PDE1/PDE5 inhibitors to a potent and selective PDE5 inhibitor for the treatment of male ED. Bioorg. Med. Chem. Lett.15 (9): 2365-9. [PMID:15837326]

4. Clerin V, Gale J, Tamimi N. (2014) Use of a tetrasubstituted pyrazolo[4,3-d]pyrimidine compound for treating diabetic nephropathy. Patent number: WO-2014064566-A1. Assignee: Pfizer Inc.. Priority date: 23/10/2012. Publication date: 01/05/2014.

5. Corbin JD, Turko IV, Beasley A, Francis SH. (2000) Phosphorylation of phosphodiesterase-5 by cyclic nucleotide-dependent protein kinase alters its catalytic and allosteric cGMP-binding activities. Eur. J. Biochem.267 (9): 2760-7. [PMID:10785399]

6. Hughes RO, Walker JK, Rogier DJ, Heasley SE, Blevis-Bal RM, Benson AG, Jacobsen EJ, Cubbage JW, Fobian YM, Owen DR et al.. (2009) Optimization of the aminopyridopyrazinones class of PDE5 inhibitors: discovery of 3-[(trans-4-hydroxycyclohexyl)amino]-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2(1H)-one. Bioorg. Med. Chem. Lett.19 (17): 5209-13. [PMID:19631533]

7. Mochida H, Takagi M, Inoue H, Noto T, Yano K, Fujishige K, Sasaki T, Yuasa K, Kotera J, Omori K et al.. (2002) Enzymological and pharmacological profile of T-0156, a potent and selective phosphodiesterase type 5 inhibitor. Eur. J. Pharmacol.456 (1-3): 91-8. [PMID:12450574]

8. Mohamed HA, Girgis NM, Wilcken R, Bauer MR, Tinsley HN, Gary BD, Piazza GA, Boeckler FM, Abadi AH. (2011) Synthesis and molecular modeling of novel tetrahydro-β-carboline derivatives with phosphodiesterase 5 inhibitory and anticancer properties. J. Med. Chem.54 (2): 495-509. [PMID:21189023]

9. Rawson DJ, Ballard S, Barber C, Barker L, Beaumont K, Bunnage M, Cole S, Corless M, Denton S, Ellis D et al.. (2012) The discovery of UK-369003, a novel PDE5 inhibitor with the potential for oral bioavailability and dose-proportional pharmacokinetics. Bioorg. Med. Chem.20 (1): 498-509. [PMID:22100260]

10. Turko IV, Ballard SA, Francis SH, Corbin JD. (1999) Inhibition of cyclic GMP-binding cyclic GMP-specific phosphodiesterase (Type 5) by sildenafil and related compounds. Mol. Pharmacol.56 (1): 124-30. [PMID:10385692]

11. Vemulapalli S, Watkins RW, Chintala M, Davis H, Ahn HS, Fawzi A, Tulshian D, Chiu P, Chatterjee M, Lin CC et al.. (1996) Antiplatelet and antiproliferative effects of SCH 51866, a novel type 1 and type 5 phosphodiesterase inhibitor. J. Cardiovasc. Pharmacol.28 (6): 862-9. [PMID:8961086]

12. Venhuis BJ, Zomer G, Hamzink M, Meiring HD, Aubin Y, de Kaste D. (2011) The identification of a nitrosated prodrug of the PDE-5 inhibitor aildenafil in a dietary supplement: a Viagra with a pop. J Pharm Biomed Anal54 (4): 735-41. [PMID:21145686]

13. Wang G, Liu Z, Chen T, Wang Z, Yang H, Zheng M, Ren J, Tian G, Yang X, Li L et al.. (2012) Design, synthesis, and pharmacological evaluation of monocyclic pyrimidinones as novel inhibitors of PDE5. J. Med. Chem.55 (23): 10540-50. [PMID:23137303]

How to cite this page

Phosphodiesterases, 3',5'-cyclic nucleotide (PDEs): phosphodiesterase 5A. Last modified on 21/04/2017. Accessed on 22/10/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1304.