Target Information

Target General Infomation
Target ID
T07663
Former ID
TTDS00296
Target Name
CGMP-specific 3',5'-cyclic phosphodiesterase
Gene Name
PDE5A
Synonyms
CGB-PDE; CGMP-binding cGMP-specific phosphodiesterase; Phosphodiesterase 5; PDE5A
Target Type
Successful
Disease Angina pectoris [ICD9: 413; ICD10: I20]
Asthma [ICD10: J45]
Allergy [ICD9: 995.3; ICD10: T78.4]
Colorectal cancer [ICD9: 153, 154; ICD10: C18-C21]
Cardiovascular disorder [ICD10: I00-I99]
Chronic obstructive pulmonary disease; Raynaud's disease [ICD9:490-492, 494-496, 443; ICD10: J40-J44, J47, I73.0]
Erectile dysfunction [ICD9: 302.72, 607.84; ICD10: F52.2, N48.4]
Erectile dysfunction; Hypertension; Raynaud's disease [ICD9:302.72, 607.84, 401, 443; ICD10: F52.2, N48.4, I10-I16, I73.0]
Hypertension [ICD9: 401; ICD10: I10-I16]
Spasm [ICD9: 728.85; ICD10: R25.2]
Unspecified [ICD code not available]
Function
Plays a role insignal transduction by regulating the intracellular concentration of cyclic nucleotides. This phosphodiesterase catalyzes the specific hydrolysis of cGMP to 5'- GMP.
BioChemical Class
Phosphoric diester hydrolases
Target Validation
T07663
UniProt ID
O76074
EC Number
EC 3.1.4.35
Sequence
MERAGPSFGQQRQQQQPQQQKQQQRDQDSVEAWLDDHWDFTFSYFVRKATREMVNAWFAE
RVHTIPVCKEGIRGHTESCSCPLQQSPRADNSAPGTPTRKISASEFDRPLRPIVVKDSEG
TVSFLSDSEKKEQMPLTPPRFDHDEGDQCSRLLELVKDISSHLDVTALCHKIFLHIHGLI
SADRYSLFLVCEDSSNDKFLISRLFDVAEGSTLEEVSNNCIRLEWNKGIVGHVAALGEPL
NIKDAYEDPRFNAEVDQITGYKTQSILCMPIKNHREEVVGVAQAINKKSGNGGTFTEKDE
KDFAAYLAFCGIVLHNAQLYETSLLENKRNQVLLDLASLIFEEQQSLEVILKKIAATIIS
FMQVQKCTIFIVDEDCSDSFSSVFHMECEELEKSSDTLTREHDANKINYMYAQYVKNTME
PLNIPDVSKDKRFPWTTENTGNVNQQCIRSLLCTPIKNGKKNKVIGVCQLVNKMEENTGK
VKPFNRNDEQFLEAFVIFCGLGIQNTQMYEAVERAMAKQMVTLEVLSYHASAAEEETREL
QSLAAAVVPSAQTLKITDFSFSDFELSDLETALCTIRMFTDLNLVQNFQMKHEVLCRWIL
SVKKNYRKNVAYHNWRHAFNTAQCMFAALKAGKIQNKLTDLEILALLIAALSHDLDHRGV
NNSYIQRSEHPLAQLYCHSIMEHHHFDQCLMILNSPGNQILSGLSIEEYKTTLKIIKQAI
LATDLALYIKRRGEFFELIRKNQFNLEDPHQKELFLAMLMTACDLSAITKPWPIQQRIAE
LVATEFFDQGDRERKELNIEPTDLMNREKKNKIPSMQVGFIDAICLQLYEALTHVSEDCF
PLLDGCRKNRQKWQALAEQQEKMLINGESGQAKRN
Structure
1RKP; 1T9R; 1T9S; 1TBF; 1UDT; 1UDU; 1UHO; 1XOZ; 1XP0;2CHM; 2H40; 2H42; 2H44; 2XSS; 3B2R; 3BJC; 3HC8; 3HDZ; 3JWQ; 3JWR; 3LFV; 3MF0; 3SHY; 3SHZ; 3SIE; 3TGE; 3TGG; 3TSE; 3TSF; 4G2W; 4G2Y; 4I9Z; 4IA0; 4MD6; 1RKP; 1T9R; 1T9S; 1TBF; 1UDT; 1UDU; 1UHO; 1XOZ; 1XP0; 2CHM; 2H40; 2H42; 2H44; 2XSS; 3B2R; 3BJC; 3HC8; 3HDZ; 3JWQ; 3JWR; 3LFV; 3MF0; 3SHY; 3SHZ; 3SIE; 3TGE; 3TGG; 3TSE; 3TSF; 4G2W; 4G2Y; 4I9Z; 4IA0; 4MD6
Drugs and Mode of Action
Drug(s) Avanafil Drug Info Approved Erectile dysfunction [1], [2]
Dipyridamole Drug Info Approved Hypertension [3], [4]
Papaverine Drug Info Approved Spasm [5]
Sildenafil Drug Info Approved Erectile dysfunction [6], [7]
Tadalafil Drug Info Approved Erectile dysfunction [8], [9]
Udenafil Drug Info Approved Erectile dysfunction [10]
Vardenafil Drug Info Approved Erectile dysfunction [8], [11]
EXISULIND Drug Info Phase 3 Colorectal cancer [12]
ICARIIN Drug Info Phase 3 Discovery agent [13]
PF-489791 Drug Info Phase 2 Chronic obstructive pulmonary disease; Raynaud's disease [14]
ROLIPRAM Drug Info Phase 2 Discovery agent [15], [16]
UK-371800 Drug Info Phase 1 Erectile dysfunction [17]
BRL-61063 Drug Info Discontinued in Phase 2 Allergy [18]
DASANTAFIL Drug Info Discontinued in Phase 2 Erectile dysfunction [19]
E-4021 Drug Info Discontinued in Phase 2 Cardiovascular disorder [20]
EMR-62203 Drug Info Discontinued in Phase 2 Erectile dysfunction [21]
SINITRODIL Drug Info Discontinued in Phase 2 Angina pectoris [22]
SLX-2101 Drug Info Discontinued in Phase 2 Erectile dysfunction; Hypertension; Raynaud's disease [23]
UK-369003 Drug Info Discontinued in Phase 1/2 Erectile dysfunction [24], [25]
FR-229934 Drug Info Terminated Erectile dysfunction [26]
IMAZODAN Drug Info Terminated Discovery agent [27]
SKF-96231 Drug Info Terminated Asthma [28]
Trequinsin Drug Info Terminated Discovery agent [29]
ZAPRINAST Drug Info Terminated Discovery agent [30], [31]
Inhibitor 3,7-Bis(2-hydroxyethyl)icaritin Drug Info [32]
3-ISOBUTYL-1-METHYLXANTHINE Drug Info [33]
7-(2-Hydroxyethyl)-3-O-rhamnosylicariin Drug Info [32]
8-prenylapigenin Drug Info [32]
8-prenylquercetin Drug Info [32]
Aom-0890 Drug Info [34]
Benzo[1,3]dioxol-5-ylmethyl-quinazolin-4-yl-amine Drug Info [35]
BRL-61063 Drug Info [36]
Cartazolate Drug Info [37]
CKD-533 Drug Info [34]
DASANTAFIL Drug Info [38]
E-4021 Drug Info [39]
EMR-62203 Drug Info [40]
FR-229934 Drug Info [41]
Gamma-Glutamyl[S-(2-Iodobenzyl)Cysteinyl]Glycine Drug Info [42]
Guanosine-5'-Monophosphate Drug Info [42]
ICARIIN Drug Info [32]
Icariside II Drug Info [32]
IMAZODAN Drug Info [43]
KURAIDIN Drug Info [44]
KURARINOL Drug Info [44]
LORNEIC ACID A Drug Info [45]
Papaverine Drug Info [46]
PF-489791 Drug Info [47]
ROLIPRAM Drug Info [35]
SCH-57726 Drug Info [48]
SCH51866 Drug Info [49]
Sildenafil Drug Info [50], [51], [52], [53]
SK&F-96321 Drug Info [36]
SKF-96231 Drug Info [54]
SLX-2101 Drug Info [55]
SOPHOFLAVESCENOL Drug Info [44]
SOPHORAFLAVANONE B Drug Info [32]
T0156 Drug Info [56]
Tadalafil Drug Info [57], [51], [58]
TPN-729 Drug Info [34]
Trequinsin Drug Info [59]
Udenafil Drug Info [60]
UK-369003 Drug Info [61], [62]
UK-371800 Drug Info [17]
ZAPRINAST Drug Info [63]
Modulator Avanafil Drug Info [38]
Dipyridamole Drug Info
EXISULIND Drug Info [64]
RWJ-387273 Drug Info
SINITRODIL Drug Info [38]
Binder Vardenafil Drug Info [65]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway Purine metabolism
cGMP-PKG signaling pathway
NetPath Pathway TGF_beta_Receptor Signaling Pathway
Reactome cGMP effects
References
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REF 2(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7448).
REF 3(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4807).
REF 4Inhibition of platelet activation and aggregation. Handb Exp Pharmacol. 2005;(170):443-62.
REF 5Drug information of Papaverine, 2008. eduDrugs.
REF 6(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4743).
REF 7Pharmacologic therapeutics for cardiac reperfusion injury. Expert Opin Emerg Drugs. 2007 Sep;12(3):367-88.
REF 8Designing drugs for the treatment of female sexual dysfunction. Drug Discov Today. 2007 Sep;12(17-18):757-66. Epub 2007 Aug 27.
REF 9(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7299).
REF 10Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77. Epub 2007 Feb 20.
REF 11(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7320).
REF 12ClinicalTrials.gov (NCT00085826) A Phase III Study of the Efficacy of Taxotere/Aptosyn Versus Taxotere/Placebo in Non-Small Cell Lung Cancer Patients. U.S. National Institutes of Health.
REF 13ClinicalTrials.gov (NCT01979133) Study of Icariin for Bipolar Disorder and Co-Occurring Substance Use Disorders. U.S. National Institutes of Health.
REF 14Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800025495)
REF 15ClinicalTrials.gov (NCT00011375) Rolipram to Treat Multiple Sclerosis. U.S. National Institutes of Health.
REF 16(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5260).
REF 17Bioorg Med Chem Lett. 2008 Dec 1;18(23):6033-6. Epub 2008 Oct 11.Highly potent and selective chiral inhibitors of PDE5: an illustration of Pfeiffer's rule.
REF 18Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004678)
REF 19Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800018967)
REF 20Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004019)
REF 21Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800018868)
REF 22Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800005482)
REF 23Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800022583)
REF 24(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6558).
REF 25Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800017097)
REF 26Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800014897)
REF 27Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000379)
REF 28Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003084)
REF 29Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000447)
REF 30(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2919).
REF 31Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000060)
REF 32J Nat Prod. 2008 Sep;71(9):1513-7. Epub 2008 Sep 9.Potent inhibition of human phosphodiesterase-5 by icariin derivatives.
REF 33The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
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REF 35J Med Chem. 1994 Jun 24;37(13):2106-11.Cyclic GMP phosphodiesterase inhibitors. 2. Requirement of 6-substitution of quinazoline derivatives for potent and selective inhibitory activity.
REF 36J Med Chem. 1994 Feb 18;37(4):476-85.Inhibition of cyclic nucleotide phosphodiesterase by derivatives of 1,3-bis(cyclopropylmethyl)xanthine.
REF 37J Med Chem. 2001 Mar 29;44(7):1025-7.Substituted pyrazolopyridines as potent and selective PDE5 inhibitors: potential agents for treatment of erectile dysfunction.
REF 38Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
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REF 40WO patent application no. 2006,0180,88, Use of a pde 5 inhibitor for treating and preventing hypopigmentary disorders.
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REF 43J Med Chem. 1984 Sep;27(9):1099-101.Cardiotonic agents. 1. 4,5-Dihydro-6-[4-(1H-imidazol-1-yl)phenyl]-3 (2H)-pyridazinones: novel positive inotropic agents for the treatment of congestive heart failure.
REF 44Bioorg Med Chem Lett. 2002 Sep 2;12(17):2313-6.A prenylated flavonol, sophoflavescenol: a potent and selective inhibitor of cGMP phosphodiesterase 5.
REF 45J Nat Prod. 2009 Nov;72(11):2046-8.Lorneic acids, trialkyl-substituted aromatic acids from a marine-derived actinomycete.
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REF 47Highlights of the society for medicinesresearch symposium held december 10th 2009 at the national heart and lung institute, London, UK. Drugs of the Future 2010, 35(4): 349-358.
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REF 49Antiplatelet and antiproliferative effects of SCH 51866, a novel type 1 and type 5 phosphodiesterase inhibitor. J Cardiovasc Pharmacol. 1996 Dec;28(6):862-9.
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REF 51Phosphodiesterase type 5 inhibitors for the treatment of erectile dysfunction in patients with diabetes mellitus. Int J Impot Res. 2002 Dec;14(6):466-71.
REF 52Knockouts model the 100 best-selling drugs--will they model the next 100? Nat Rev Drug Discov. 2003 Jan;2(1):38-51.
REF 53cGMP-hydrolytic activity and its inhibition by sildenafil in normal and failing human and mouse myocardium. J Pharmacol Exp Ther. 2009 Jun 22.
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REF 55Novel phosphodiesterase-5 (PDE5) inhibitors in the alleviation of erectile dysfunction due to diabetes and ageing-induced oxidative stress. Expert Opin Investig Drugs. 2008 Jun;17(6):855-64.
REF 56Enzymological and pharmacological profile of T-0156, a potent and selective phosphodiesterase type 5 inhibitor. Eur J Pharmacol. 2002 Dec 5;456(1-3):91-8.
REF 57Tadalafil (Cialis) for men with erectile dysfunction. Int J Clin Pract. 2002 May;56(4):300-4.
REF 58Pulmonary arterial hypertension: the most devastating vascular complication of systemic sclerosis. Rheumatology (Oxford). 2009 Jun;48 Suppl 3:iii25-31.
REF 59J Med Chem. 1989 Jul;32(7):1450-7.Inhibition of cyclic adenosine-3',5'-monophosphate phosphodiesterase from vascular smooth muscle by rolipram analogues.
REF 60Increased expression of the nitric oxide synthase gene and protein in corpus cavernosum by repeated dosing of udenafil in a rat model of chemical diabetogenesis. Asian J Androl. 2009 Jul;11(4):435-42. Epub 2009 May 25.
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REF 62Pfizer. Product Development Pipeline. March 31 2009.
REF 63J Med Chem. 2000 Jun 29;43(13):2523-9.4-(3-Chloro-4-methoxybenzyl)aminophthalazines: synthesis and inhibitory activity toward phosphodiesterase 5.
REF 64Exisulind induction of apoptosis involves guanosine 3',5'-cyclic monophosphate phosphodiesterase inhibition, protein kinase G activation, and attenuated beta-catenin. Cancer Res. 2000 Jul 1;60(13):3338-42.
REF 65The effect of vardenafil, a potent and highly selective phosphodiesterase-5 inhibitor for the treatment of erectile dysfunction, on the cardiovascular response to exercise in patients with coronary artery disease. J Am Coll Cardiol. 2002 Dec 4;40(11):2006-12.

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