Target Information

Target General Infomation
Target ID
T14342
Former ID
TTDS00317
Target Name
HIV-1 reverse transcriptase
Gene Name
pol
Synonyms
HIV-1 RT; Human immunodeficiency virus type 1 reverse transcriptase; pol
Target Type
Successful
Disease Cancer [ICD9: 140-229; ICD10: C00-C96]
Human immunodeficiency virus infection [ICD9: 279.3; ICD10: B20-B26]
Hepacivirus infections [ICD9: 070.4, 070.5, 070.70; ICD10: B17.1, B18.2]
Solid tumours [ICD9: 140-199, 210-229; ICD10: C00-D48]
Viral infections [ICD9: 054.0, 054.1, 054.2, 054.3, 075, 771.2, 052, 053; ICD10: B01, B02, A60, B00, B27, G05.1, P35.2]
BioChemical Class
Kinase
Target Validation
T14342
UniProt ID
Q69617
EC Number
EC 2.7.7.49
Sequence
MEKEGKISKIGPENPYNTPVFAIKKKDSTRWRKLVDFRELNKRTQDFWEVQLGIPHPAGL
KKKKSVTV
Drugs and Mode of Action
Drug(s) Rilpivirine Drug Info Approved Human immunodeficiency virus infection [1]
Sorivudine Drug Info Approved Viral infections [2]
PT-304 Drug Info Phase 3 Discovery agent [3]
Dideoxycytidine Drug Info Phase 2 Discovery agent [4]
Dapivirine Drug Info Phase 1/2 Human immunodeficiency virus infection [5]
TRICIRIBINE Drug Info Phase 1/2 Solid tumours [6], [7]
PT-112 Drug Info Phase 1 Cancer [8]
PT-302 Drug Info Phase 1 Discovery agent [9]
LY-73497 Drug Info Discontinued in Phase 1 Discovery agent [10]
Inhibitor 1-(1-Phenyl-propyl)-3-thiazol-2-yl-thiourea Drug Info [11]
1-(2-Furan-2-yl-ethyl)-3-thiazol-2-yl-thiourea Drug Info [12]
1-(2-Phenoxy-ethyl)-3-thiazol-2-yl-thiourea Drug Info [11]
1-(2-Phenyl-propyl)-3-thiazol-2-yl-thiourea Drug Info [12]
1-(2-Pyridin-2-yl-ethyl)-3-thiazol-2-yl-thiourea Drug Info [12]
1-(3-Phenyl-propyl)-3-thiazol-2-yl-thiourea Drug Info [12]
1-(4-Butyl-thiazol-2-yl)-3-phenethyl-thiourea Drug Info [12]
1-(4-Cyano-thiazol-2-yl)-3-phenethyl-thiourea Drug Info [12]
1-Adamantan-1-ylmethyl-3-thiazol-2-yl-thiourea Drug Info [11]
1-Benzenesulfonyl-2-nitro-benzene Drug Info [13]
1-Benzothiazol-2-yl-3-phenethyl-thiourea Drug Info [12]
1-Benzyl-3-thiazol-2-yl-thiourea Drug Info [12]
1-Furan-2-ylmethyl-3-thiazol-2-yl-thiourea Drug Info [11]
1-nitro-2-(2-nitrophenylsulfonyl)benzene Drug Info [13]
1-Phenethyl-3-[1,3,4]thiadiazol-2-yl-thiourea Drug Info [12]
1-Thiazol-2-yl-3-(2-o-tolyl-ethyl)-thiourea Drug Info [12]
1-Thiazol-2-yl-3-(2-p-tolyl-ethyl)-thiourea Drug Info [11]
10-Allyl-10H-dibenzo[b,f][1,4]oxazepin-11-one Drug Info [14]
10-Ethyl-10H-dibenzo[b,f][1,4]oxazepin-11-one Drug Info [14]
10-Isopropyl-10H-dibenzo[b,f][1,4]oxazepin-11-one Drug Info [14]
10-Propyl-10H-dibenzo[b,f][1,4]oxazepin-11-one Drug Info [14]
10-Propyl-10H-dibenzo[b,f][1,4]thiazepin-11-one Drug Info [14]
2',3'-Dideoxyadenosine Triphosphate (Ddatp) Drug Info [15]
2'-3'-dideoxy-7-deaza-guaninetriphosphate Drug Info [15]
2-Amino-6-(2-bromo-benzenesulfonyl)-benzonitrile Drug Info [13]
2-Amino-6-(2-chloro-benzenesulfonyl)-benzonitrile Drug Info [13]
2-Amino-6-(2-chloro-phenylsulfanyl)-benzonitrile Drug Info [13]
2-Amino-6-(2-cyano-benzenesulfinyl)-benzonitrile Drug Info [13]
2-Amino-6-(2-cyano-benzenesulfonyl)-benzonitrile Drug Info [13]
2-Amino-6-(2-cyano-phenylsulfanyl)-benzonitrile Drug Info [13]
2-Amino-6-(2-fluoro-benzenesulfonyl)-benzonitrile Drug Info [13]
2-Amino-6-(2-methoxy-phenylsulfanyl)-benzonitrile Drug Info [13]
2-Amino-6-(3-bromo-benzenesulfinyl)-benzonitrile Drug Info [13]
2-Amino-6-(3-bromo-benzenesulfonyl)-benzonitrile Drug Info [13]
2-Amino-6-(3-bromo-phenylsulfanyl)-benzonitrile Drug Info [13]
2-Amino-6-(3-chloro-benzenesulfonyl)-benzonitrile Drug Info [13]
2-Amino-6-(3-chloro-phenylsulfanyl)-benzonitrile Drug Info [13]
2-Amino-6-(3-cyano-benzenesulfonyl)-benzonitrile Drug Info [13]
2-Amino-6-(3-cyano-phenylsulfanyl)-benzonitrile Drug Info [13]
2-Amino-6-(3-fluoro-phenylsulfanyl)-benzonitrile Drug Info [13]
2-Amino-6-(3-methoxy-phenylsulfanyl)-benzonitrile Drug Info [13]
2-Amino-6-(4-chloro-phenylsulfanyl)-benzonitrile Drug Info [13]
2-Amino-6-(naphthalene-1-sulfonyl)-benzonitrile Drug Info [13]
2-Amino-6-(naphthalene-2-sulfonyl)-benzonitrile Drug Info [13]
2-Amino-6-(toluene-2-sulfonyl)-benzonitrile Drug Info [13]
2-Amino-6-(toluene-3-sulfinyl)-benzonitrile Drug Info [13]
2-Amino-6-(toluene-3-sulfonyl)-benzonitrile Drug Info [13]
2-Amino-6-(toluene-4-sulfonyl)-benzonitrile Drug Info [13]
2-Amino-6-benzenesulfonyl-benzonitrile Drug Info [13]
2-Amino-6-m-tolylsulfanyl-benzonitrile Drug Info [13]
2-Amino-6-p-tolylsulfanyl-benzonitrile Drug Info [13]
2-Amino-6-phenylsulfanyl-benzonitrile Drug Info [13]
2-Benzylsulfanyl-6-chloro-pyrimidin-4-ylamine Drug Info [16]
3'thiacytidine Drug Info [17]
3-Benzylamino-5-ethyl-6-methyl-1H-pyridin-2-one Drug Info [18]
6-Benzyl-2-cyclohexylsulfanyl-3H-pyrimidin-4-one Drug Info [19]
6-Benzyl-2-cyclopentylsulfanyl-3H-pyrimidin-4-one Drug Info [20]
6-Benzyl-2-isobutylsulfanyl-3H-pyrimidin-4-one Drug Info [19]
6-Benzyl-2-sec-butylsulfanyl-3H-pyrimidin-4-one Drug Info [20]
Benzimidazole 5-carboxamide Drug Info [5]
Benzothiadiazines Drug Info [5]
CORILAGIN Drug Info [21]
Cyclosporin A analogue Drug Info [22]
Dapivirine Drug Info [5]
DdC Drug Info [23]
DdI Drug Info [23]
Deoxyfluorothymidine Drug Info [17]
DEOXYTHYMIDINE_TRIPHOSPHATE Drug Info [15]
Dideoxycytidine Drug Info [17]
Dihydropyrone Drug Info [5]
EPIGALOCATECHIN GALLATE Drug Info [24]
Ethyl 1-[(1H-benzimidazol-2(3H)one-5-yl)sulfonyl]-1H-pyrrole-2-carboxylate Drug Info [25]
Ethyl 1-[(1H-benzimidazol-5(6)-yl)sulfonyl]-1H-pyrrole-2-carboxylate Drug Info [25]
Ethyl 1-[(1H-benzotriazol-5(6)-yl)sulfonyl]-1H-pyrrole-2-carboxylate Drug Info [25]
Fullerene Derivative Drug Info [26]
HEPT Drug Info [27]
HI-172 Drug Info [28]
HI-236 Drug Info [29]
HI-240 Drug Info [30]
HI-241 Drug Info [29]
HI-242 Drug Info [29]
HI-244 Drug Info [11]
HI-280 Drug Info [28]
HI-281 Drug Info [28]
HI-443 Drug Info [30]
HI-445 Drug Info [28]
Indole N -acetamide Drug Info [5]
ISODISPAR B Drug Info [31]
LY-73497 Drug Info [12]
NSC-380292 Drug Info [32]
PT-101 Drug Info [12]
PT-102 Drug Info [29]
PT-103 Drug Info [12]
PT-104 Drug Info [33]
PT-106 Drug Info [12]
PT-108 Drug Info [12]
PT-109 Drug Info [33]
PT-110 Drug Info [33]
PT-112 Drug Info [33]
PT-113 Drug Info [33]
PT-114 Drug Info [33]
PT-115 Drug Info [33]
PT-302 Drug Info [12]
PT-304 Drug Info [12]
PT-306 Drug Info [12]
PT-307 Drug Info [12]
PT-308 Drug Info [12]
PT-309 Drug Info [12]
PT-310 Drug Info [12]
PT-311 Drug Info [12]
PT-312 Drug Info [12]
PT-313 Drug Info [12]
PT-314 Drug Info [12]
PT-315 Drug Info [12]
PT-316 Drug Info [12]
PT-317 Drug Info [12]
PT-319 Drug Info [12]
PT-320 Drug Info [12]
PT-322 Drug Info [12]
R-87027 Drug Info [34]
Rilpivirine Drug Info [5]
RTI-20 Drug Info [35]
Tetrahydroimidazo[4,5,1-jk]-[1,4]benzodiazepin-2(1H)-one Drug Info [36]
TIBO Drug Info [37]
TRICIRIBINE Drug Info [38]
UK-129485 Drug Info [39]
[(40-OH) MeLeu]4-CsA derivatives Drug Info [22]
[(40-OH)MeLeu]4-Cyclosporin A Drug Info [22]
[(D)MeSer]3-[(40-OH) MeLeu]4-Cyclosporin A Drug Info [22]
Modulator Sorivudine Drug Info [40], [41]
References
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REF 2Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
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REF 4ClinicalTrials.gov (NCT00000678) Dideoxycytidine ( Ro 24-2027 ) A Randomized, Open-Label, Comparative Study of Dideoxycytidine ( ddC ) Versus Zidovudine ( AZT ) in Patients With AIDS or Advanced ARC Who Have Received Long-Term AZT Therapy.. U.S. National Institutes of Health.
REF 5Emerging antiviral drugs. Expert Opin Emerg Drugs. 2008 Sep;13(3):393-416.
REF 6ClinicalTrials.gov (NCT01697293) Triciribine Phosphate in Breast Cancer. U.S. National Institutes of Health.
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REF 8ClinicalTrials.gov (NCT02266745) A Phase 1 Study of PT-112 Injection in Subjects With Advanced Solid Tumors. U.S. National Institutes of Health.
REF 9ClinicalTrials.gov (NCT00964262) A Study to Evaluate Safety and Pharmacokinetics/Pharmacodynamics of Sustained Release(SR) Exenatide. U.S. National Institutes of Health.
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REF 11Bioorg Med Chem Lett. 2001 Feb 26;11(4):523-8.Anti-HIV activity of aromatic and heterocyclic thiazolyl thiourea compounds.
REF 12J Med Chem. 1995 Dec 8;38(25):4929-36.Phenethylthiazolethiourea (PETT) compounds, a new class of HIV-1 reverse transcriptase inhibitors. 1. Synthesis and basic structure-activity relationship studiesof PETT analogs.
REF 13J Med Chem. 2001 Jun 7;44(12):1866-82.2-Amino-6-arylsulfonylbenzonitriles as non-nucleoside reverse transcriptase inhibitors of HIV-1.
REF 14J Med Chem. 1992 May 15;35(10):1887-97.Novel non-nucleoside inhibitors of HIV-1 reverse transcriptase. 2. Tricyclic pyridobenzoxazepinones and dibenzoxazepinones.
REF 15J Med Chem. 2005 Apr 7;48(7):2695-700.Synthesis of 2',3'-dideoxynucleoside 5'-alpha-P-borano-beta,gamma-(difluoromethylene)triphosphates and their inhibition of HIV-1 reverse transcriptase.
REF 16J Med Chem. 1998 Sep 24;41(20):3793-803.Pyrimidine thioethers: a novel class of HIV-1 reverse transcriptase inhibitors with activity against BHAP-resistant HIV.
REF 17Current use of anti-HIV drugs in AIDS. J Antimicrob Chemother. 1993 Jul;32 Suppl A:133-8.
REF 18J Med Chem. 1992 Oct 16;35(21):3792-802.Synthesis and evaluation of 2-pyridinone derivatives as HIV-1-specific reverse transcriptase inhibitors. 2. Analogues of 3-aminopyridin-2(1H)-one.
REF 19J Med Chem. 1995 Aug 18;38(17):3258-63.Synthesis and anti-HIV-1 activity of thio analogues of dihydroalkoxybenzyloxopyrimidines.
REF 20J Med Chem. 1999 Feb 25;42(4):619-27.5-Alkyl-2-(alkylthio)-6-(2,6-dihalophenylmethyl)-3, 4-dihydropyrimidin-4(3H)-ones: novel potent and selective dihydro-alkoxy-benzyl-oxopyrimidine derivatives.
REF 21HIV and reverse transcriptase inhibition by tanninsOriginal Research. Bioorg. Med. Chem. Lett. 2(12):1529-1534 (1992).
REF 22Bioorg Med Chem Lett. 2003 Dec 15;13(24):4415-9.Synthesis of non-immunosuppressive cyclophilin-Binding cyclosporin A derivatives as potential anti-HIV-1 drugs.
REF 23A peptide inhibitor of HIV-1 reverse transcriptase using alpha,beta-dehydro residues: a structure-based computer model. J Biomol Struct Dyn. 1998 Oct;16(2):347-54.
REF 24Bioorg Med Chem Lett. 2001 Oct 22;11(20):2763-7.Simplified catechin-gallate inhibitors of HIV-1 reverse transcriptase.
REF 25Computer-assisted design, synthesis and biological evaluation of novel pyrrolyl heteroaryl sulfones targeted at HIV-1 reverse transcriptase as non-nucleoside inhibitors. Bioorg Med Chem. 2000 Sep;8(9):2305-9.
REF 26Bioorg Med Chem Lett. 2005 Feb 15;15(4):1107-9.Human immunodeficiency virus-reverse transcriptase inhibition and hepatitis C virus RNA-dependent RNA polymerase inhibition activities of fullerene derivatives.
REF 27Bioorg Med Chem Lett. 2004 Jun 21;14(12):3173-6.5-Alkyl-2-[(aryl and alkyloxylcarbonylmethyl)thio]-6-(1-naphthylmethyl) pyrimidin-4(3H)-ones as an unique HIV reverse transcriptase inhibitors of S-DABO series.
REF 28Bioorg Med Chem Lett. 1999 Jun 7;9(11):1593-8.Rational design of N-[2-(2,5-dimethoxyphenylethyl)]-N'-[2-(5-bromopyridyl)]-thiourea (HI-236) as a potent non-nucleoside inhibitor of drug-resistant human immunodeficiency virus.
REF 29Bioorg Med Chem Lett. 2000 Jan 3;10(1):87-90.Antioxidant function of phenethyl-5-bromo-pyridyl thiourea compounds with potent anti-HIV activity.
REF 30Bioorg Med Chem Lett. 1999 Dec 20;9(24):3411-6.N'-[2-(2-thiophene)ethyl]-N'-[2-(5-bromopyridyl)] thiourea as a potent inhibitor of NNI-resistant and multidrug-resistant human immunodeficiency virus-1.
REF 31Bioorg Med Chem Lett. 2005 Oct 15;15(20):4447-50.4-Phenylcoumarins as HIV transcription inhibitors.
REF 32Bioorg Med Chem Lett. 2006 Jun 1;16(11):3034-8. Epub 2006 Mar 9.New HIV-1 reverse transcriptase inhibitors based on a tricyclic benzothiophene scaffold: synthesis, resolution, and inhibitory activity.
REF 33J Med Chem. 1996 Oct 11;39(21):4261-74.Phenethylthiazolylthiourea (PETT) compounds as a new class of HIV-1 reverse transcriptase inhibitors. 2. Synthesis and further structure-activity relationship studies of PETT analogs.
REF 34J Med Chem. 1998 Dec 17;41(26):5272-86.Prediction of binding affinities for TIBO inhibitors of HIV-1 reverse transcriptase using Monte Carlo simulations in a linear response method.
REF 35J Med Chem. 1991 Jul;34(7):2231-41.Novel non-nucleoside inhibitors of HIV-1 reverse transcriptase. 1. Tricyclic pyridobenzo- and dipyridodiazepinones.
REF 36Chimeric human immunodeficiency virus type 1/type 2 reverse transcriptases display reversed sensitivity to nonnucleoside analog inhibitors. Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9878-82.
REF 37J Med Chem. 1996 May 24;39(11):2129-40.Comparative molecular moment analysis (CoMMA): 3D-QSAR without molecular superposition.
REF 38J Med Chem. 2005 Jun 2;48(11):3840-51.Design, synthesis and antiviral activity of novel 4,5-disubstituted 7-(beta-D-ribofuranosyl)pyrrolo[2,3-d][1,2,3]triazines and the novel 3-amino-5-methyl-1-(beta-D-ribofuranosyl)- and 3-amino-5-methyl-1-(2-deoxy-beta-D-ribofuranosyl)-1,5-dihydro-1,4,5,6,7,8-hexaazaacenaphthylene as analogues of triciribine.
REF 39Imidazo[2??3??:6,5]dipyrido[3,2-b:2??3??e]-1,4-diazepines: non-nucleoside HIV-1 reverse transcriptase inhibitors with greater enzyme affinity than nevirapine, Bioorg. Med. Chem. Lett. 2(12):1745-1750(1992).
REF 40New antivirals with activity against varicella-zoster virus. Ann Neurol. 1994;35 Suppl:S69-72.
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