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 [532210], [542472]
Dipyridamole Drug Info Approved Hypertension [468038], [536214]
Papaverine Drug Info Approved Spasm [550750]
Sildenafil Drug Info Approved Erectile dysfunction [467986], [536497]
Tadalafil Drug Info Approved Erectile dysfunction [536493], [542319]
Udenafil Drug Info Approved Erectile dysfunction [536361]
Vardenafil Drug Info Approved Erectile dysfunction [536493], [542344]
EXISULIND Drug Info Phase 3 Colorectal cancer [521600]
ICARIIN Drug Info Phase 3 Discovery agent [524514]
PF-489791 Drug Info Phase 2 Chronic obstructive pulmonary disease; Raynaud's disease [548422]
ROLIPRAM Drug Info Phase 2 Discovery agent [521483], [540724]
UK-371800 Drug Info Phase 1 Erectile dysfunction [529766]
BRL-61063 Drug Info Discontinued in Phase 2 Allergy [545780]
DASANTAFIL Drug Info Discontinued in Phase 2 Erectile dysfunction [547746]
E-4021 Drug Info Discontinued in Phase 2 Cardiovascular disorder [545643]
EMR-62203 Drug Info Discontinued in Phase 2 Erectile dysfunction [547732]
SINITRODIL Drug Info Discontinued in Phase 2 Angina pectoris [545952]
SLX-2101 Drug Info Discontinued in Phase 2 Erectile dysfunction; Hypertension; Raynaud's disease [548157]
UK-369003 Drug Info Discontinued in Phase 1/2 Erectile dysfunction [541682], [547526]
FR-229934 Drug Info Terminated Erectile dysfunction [547290]
IMAZODAN Drug Info Terminated Discovery agent [544637]
SKF-96231 Drug Info Terminated Asthma [545385]
Trequinsin Drug Info Terminated Discovery agent [544656]
ZAPRINAST Drug Info Terminated Discovery agent [539935], [544527]
Inhibitor 3,7-Bis(2-hydroxyethyl)icaritin Drug Info [529676]
3-ISOBUTYL-1-METHYLXANTHINE Drug Info [551374]
7-(2-Hydroxyethyl)-3-O-rhamnosylicariin Drug Info [529676]
8-prenylapigenin Drug Info [529676]
8-prenylquercetin Drug Info [529676]
Aom-0890 Drug Info [543407]
Benzo[1,3]dioxol-5-ylmethyl-quinazolin-4-yl-amine Drug Info [533856]
BRL-61063 Drug Info [533908]
Cartazolate Drug Info [526024]
CKD-533 Drug Info [543407]
DASANTAFIL Drug Info [551871]
E-4021 Drug Info [525427]
EMR-62203 Drug Info [550125]
FR-229934 Drug Info [547291]
Gamma-Glutamyl[S-(2-Iodobenzyl)Cysteinyl]Glycine Drug Info [551393]
Guanosine-5'-Monophosphate Drug Info [551393]
ICARIIN Drug Info [529676]
Icariside II Drug Info [529676]
IMAZODAN Drug Info [533555]
KURAIDIN Drug Info [526395]
KURARINOL Drug Info [526395]
LORNEIC ACID A Drug Info [530477]
Papaverine Drug Info [535712]
PF-489791 Drug Info [551982]
ROLIPRAM Drug Info [533856]
SCH-57726 Drug Info [551318]
SCH51866 Drug Info [534290]
Sildenafil Drug Info [535598], [535643], [535660], [537507]
SK&F-96321 Drug Info [533908]
SKF-96231 Drug Info [551814]
SLX-2101 Drug Info [529481]
SOPHOFLAVESCENOL Drug Info [526395]
SOPHORAFLAVANONE B Drug Info [529676]
T0156 Drug Info [526468]
Tadalafil Drug Info [535487], [535643], [537402]
TPN-729 Drug Info [543407]
Trequinsin Drug Info [533047]
Udenafil Drug Info [537372]
UK-369003 Drug Info [525340], [549974]
UK-371800 Drug Info [529766]
ZAPRINAST Drug Info [525827]
Modulator Avanafil Drug Info [551871]
Dipyridamole Drug Info
EXISULIND Drug Info [525834]
RWJ-387273 Drug Info
SINITRODIL Drug Info [551871]
Binder Vardenafil Drug Info [535626]
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
Ref 467986(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 468038(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 521483ClinicalTrials.gov (NCT00011375) Rolipram to Treat Multiple Sclerosis. U.S. National Institutes of Health.
Ref 521600ClinicalTrials.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 524514ClinicalTrials.gov (NCT01979133) Study of Icariin for Bipolar Disorder and Co-Occurring Substance Use Disorders. U.S. National Institutes of Health.
Ref 529766Bioorg 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 532210Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
Ref 536214Inhibition of platelet activation and aggregation. Handb Exp Pharmacol. 2005;(170):443-62.
Ref 536361Natural 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 536493Designing drugs for the treatment of female sexual dysfunction. Drug Discov Today. 2007 Sep;12(17-18):757-66. Epub 2007 Aug 27.
Ref 536497Pharmacologic therapeutics for cardiac reperfusion injury. Expert Opin Emerg Drugs. 2007 Sep;12(3):367-88.
Ref 539935(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 540724(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 541682(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 542319(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 542344(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 542472(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 544527Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000060)
Ref 544637Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000379)
Ref 544656Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000447)
Ref 545385Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003084)
Ref 545643Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004019)
Ref 545780Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004678)
Ref 545952Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800005482)
Ref 547290Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800014897)
Ref 547526Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800017097)
Ref 547732Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800018868)
Ref 547746Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800018967)
Ref 548157Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800022583)
Ref 548422Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800025495)
Ref 550750Drug information of Papaverine, 2008. eduDrugs.
Ref 525340ClinicalTrials.gov (NCT00457457) Pfizer. Report of Pfizer. September 2 2008.
Ref 525427Potency and mechanism of action of E4021, a type 5 phosphodiesterase isozyme-selective inhibitor, on the photoreceptor phosphodiesterase depend on the state of activation of the enzyme. Mol Pharmacol. 1999 Mar;55(3):508-14.
Ref 525827J Med Chem. 2000 Jun 29;43(13):2523-9.4-(3-Chloro-4-methoxybenzyl)aminophthalazines: synthesis and inhibitory activity toward phosphodiesterase 5.
Ref 525834Exisulind 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 526024J 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 526395Bioorg Med Chem Lett. 2002 Sep 2;12(17):2313-6.A prenylated flavonol, sophoflavescenol: a potent and selective inhibitor of cGMP phosphodiesterase 5.
Ref 526468Enzymological 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 529481Novel 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 529676J Nat Prod. 2008 Sep;71(9):1513-7. Epub 2008 Sep 9.Potent inhibition of human phosphodiesterase-5 by icariin derivatives.
Ref 529766Bioorg 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 530477J Nat Prod. 2009 Nov;72(11):2046-8.Lorneic acids, trialkyl-substituted aromatic acids from a marine-derived actinomycete.
Ref 533047J Med Chem. 1989 Jul;32(7):1450-7.Inhibition of cyclic adenosine-3',5'-monophosphate phosphodiesterase from vascular smooth muscle by rolipram analogues.
Ref 533555J 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 533856J 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 533908J Med Chem. 1994 Feb 18;37(4):476-85.Inhibition of cyclic nucleotide phosphodiesterase by derivatives of 1,3-bis(cyclopropylmethyl)xanthine.
Ref 534290Antiplatelet and antiproliferative effects of SCH 51866, a novel type 1 and type 5 phosphodiesterase inhibitor. J Cardiovasc Pharmacol. 1996 Dec;28(6):862-9.
Ref 535487Tadalafil (Cialis) for men with erectile dysfunction. Int J Clin Pract. 2002 May;56(4):300-4.
Ref 535598Efficacy and safety of sildenafil citrate (Viagra) in men with erectile dysfunction and spinal cord injury: a review. Urology. 2002 Sep;60(2 Suppl 2):49-57.
Ref 535626The 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.
Ref 535643Phosphodiesterase 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 535660Knockouts model the 100 best-selling drugs--will they model the next 100? Nat Rev Drug Discov. 2003 Jan;2(1):38-51.
Ref 535712Effects of icariin on cGMP-specific PDE5 and cAMP-specific PDE4 activities. Asian J Androl. 2003 Mar;5(1):15-8.
Ref 537372Increased 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.
Ref 537402Pulmonary arterial hypertension: the most devastating vascular complication of systemic sclerosis. Rheumatology (Oxford). 2009 Jun;48 Suppl 3:iii25-31.
Ref 537507cGMP-hydrolytic activity and its inhibition by sildenafil in normal and failing human and mouse myocardium. J Pharmacol Exp Ther. 2009 Jun 22.
Ref 543407(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. (Target id: 1304).
Ref 547291Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800014897)
Ref 549974Pfizer. Product Development Pipeline. March 31 2009.
Ref 550125WO patent application no. 2006,0180,88, Use of a pde 5 inhibitor for treating and preventing hypopigmentary disorders.
Ref 551318The Gif system as a tool in medicinal chemistry: The oxidation of Sch 57726 under GoAggIII conditions, Bioorg. Med. Chem. Lett. 7(11):1381-1386 (1997).
Ref 551374The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
Ref 551393How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
Ref 551814Analogue-based Drug Discovery II. Janos Fischer,C. Robin Ganellin. Page(150).
Ref 551871Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
Ref 551982Highlights 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.

If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.