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; Hypertension; Raynaud's disease [ICD9:302.72, 607.84, 401, 443; ICD10: F52.2, N48.4, I10-I16, I73.0]
Erectile dysfunction [ICD9: 302.72, 607.84; ICD10: F52.2, N48.4]
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
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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).
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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)
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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.
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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.
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