Resistance mutation info of drug

Drug General Information
Drug ID D0BP9C
Drug Name Etravirine Drug Info
Synonyms Intelence; DAPY deriv; Diaminopyrimidine deriv; R 165335; R165335; TMC 125; TMC125; Intelence (TN); Intelence(TM); R-165335; R165335-TMC125; TMC-125; Etravirine (JAN/USAN/INN); TMC-125/R-165335; 4-((6-amino-5-bromo-2-((4-cyanophenyl)amino)-4-pyrimidinyl)oxy)-3,5-dimethyl-benzonitrile; 4-({6-AMINO-5-BROMO-2-[(4-CYANOPHENYL)AMINO]PYRIMIDIN-4-YL}OXY)-3,5-DIMETHYLBENZONITRILE; 4-[6-amino-5-bromo-2-(4-cyanoanilino)pyrimidin-4-yl]oxy-3,5-dimethylbenzonitrile; 65B; ETR
Drug Type Small molecular drug
Structure D0BP9C
Drug Resistance Mutations
Target Name HIV Non-Nucleoside reverse transcriptase
Uniprot ID POL_HV1B1(600-1159)
Species Human immunodeficiency virus type 1 (HIV-1)
Reference Sequence PISPIETVPVKLKPGMDGPKVKQWPLTEEKIKALVEICTEMEKEGKISKIGPENPYNTPV
FAIKKKDSTKWRKLVDFRELNKRTQDFWEVQLGIPHPAGLKKKKSVTVLDVGDAYFSVPL
DEDFRKYTAFTIPSINNETPGIRYQYNVLPQGWKGSPAIFQSSMTKILEPFKKQNPDIVI
YQYMDDLYVGSDLEIGQHRTKIEELRQHLLRWGLTTPDKKHQKEPPFLWMGYELHPDKWT
VQPIVLPEKDSWTVNDIQKLVGKLNWASQIYPGIKVRQLCKLLRGTKALTEVIPLTEEAE
LELAENREILKEPVHGVYYDPSKDLIAEIQKQGQGQWTYQIYQEPFKNLKTGKYARMRGA
HTNDVKQLTEAVQKITTESIVIWGKTPKFKLPIQKETWETWWTEYWQATWIPEWEFVNTP
PLVKLWYQLEKEPIVGAETFYVDGAANRETKLGKAGYVTNKGRQKVVPLTNTTNQKTELQ
AIYLALQDSGLEVNIVTDSQYALGIIQAQPDKSESELVNQIIEQLIKKEKVYLAWVPAHK
GIGGNEQVDKLVSAGIRKIL [Human immunodeficiency virus type 1 (H
IV-1)]
Targeted Disease HIV infection
Drug Resistance Mutations
Mutation info Missense: Y188L [555484]
Level of Resistance Reduce susceptibility to ETR
Mutation info Missense: K101P [555757]
Level of Resistance Reduce ETR susceptibility 5 fold
Mutation info Missense: L100I [555479]
Level of Resistance Intermediate resistance
Mutation info Missense: Y181C [555757]
Level of Resistance Reduce ETR susceptibility 5 fold
Mutation info Missense: E138K [555773], [555809], [555828]
Level of Resistance Reduce ETR susceptibility about 2 fold
Mutation info Missense: K101E [555479], [555757], [555773]
Level of Resistance Reduce ETR susceptibility 1-5 fold
Mutation info Missense: G190E [555572], [555737], [555925]
Level of Resistance Confer high-level resistance to ETR
Mutation info Missense: V179E [555510], [555701], [555925]
Level of Resistance Confer low-level resistance to ETR
Mutation info Missense: K238T [555510], [555581], [555925]
Level of Resistance Reduce susceptibility to ETR
Mutation info Missense: G190Q [555509], [555962]
Level of Resistance Reduce susceptibility to ETR
Mutation info Missense: V179D [555701], [555962]
Level of Resistance Reduce ETR susceptibility 2-3 fold
Mutation info Missense: K238N [555726], [555925]
Level of Resistance Reduce susceptibility to ETR
Mutation info Missense: V179F [555773], [555840]
Level of Resistance Low-level resistance
Mutation info Missense: L100V [555914], [555925]
Level of Resistance Reduce susceptibility to ETR
Mutation info Missense: E138G [556228], [556242]
Mutation info Missense: E138Q [556228], [556242]
Mutation info Missense: G190A [556228], [556242]
Mutation info Missense: G190S [556228], [556242]
Mutation info Missense: M230L [556228], [556242]
Level of Resistance Intermediate resistance
Mutation info Missense: V179F + Y181C [556228], [556242]
Level of Resistance Low-level resistance
Mutation info Missense: Y181F [556228], [556242]
Level of Resistance Low-level resistance
Mutation info Missense: Y181G [556228], [556242]
Level of Resistance Low-level resistance
Mutation info Missense: Y181I [556228], [556242]
Level of Resistance High-level resistance
Mutation info Missense: Y181S [556228], [556242]
Level of Resistance Low-level resistance
Mutation info Missense: Y181V [556228], [556242]
Level of Resistance High-level resistance
Mutation info Missense: E138A [555809]
Level of Resistance Reduce ETR susceptibility about 2 fold
Mutation info Missense: E138R [556038]
Level of Resistance Reduce ETR susceptibility 2-3 fold
Mutation info Missense: F227C [556038]
Level of Resistance Reduce ETR susceptibility 4-5 fold
Mutation info Missense: M230I [556038]
Level of Resistance Reduce ETR susceptibility 9 fold
References
Ref 5299412008 FDA drug approvals. Nat Rev Drug Discov. 2009 Feb;8(2):93-6.
Ref 536833Emerging antiviral drugs. Expert Opin Emerg Drugs. 2008 Sep;13(3):393-416.
Ref 555479Human immunodeficiency virus type 1 mutations selected in patients failing efavirenz combination therapy. Antimicrob Agents Chemother. 2000 Sep;44(9):2475-84.
Ref 555484Genotypic correlates of phenotypic resistance to efavirenz in virus isolates from patients failing nonnucleoside reverse transcriptase inhibitor therapy. J Virol. 2001 Jun;75(11):4999-5008.
Ref 555509Amino acid substitutions at position 190 of human immunodeficiency virus type 1 reverse transcriptase increase susceptibility to delavirdine and impair virus replication. J Virol. 2003 Jan;77(2):1512-23.
Ref 555510Human immunodeficiency virus reverse transcriptase and protease sequence database. Nucleic Acids Res. 2003 Jan 1;31(1):298-303.
Ref 555572TMC125 displays a high genetic barrier to the development of resistance: evidence from in vitro selection experiments. J Virol. 2005 Oct;79(20):12773-82.
Ref 555581The K101P and K103R/V179D mutations in human immunodeficiency virus type 1 reverse transcriptase confer resistance to nonnucleoside reverse transcriptase inhibitors. Antimicrob Agents Chemother. 2006 Jan;50(1):351-4.
Ref 555701Compilation and prevalence of mutations associated with resistance to non-nucleoside reverse transcriptase inhibitors. Antivir Ther. 2009;14(1):103-9.
Ref 555726Nonpolymorphic human immunodeficiency virus type 1 protease and reverse transcriptase treatment-selected mutations. Antimicrob Agents Chemother. 2009 Nov;53(11):4869-78. doi: 10.1128/AAC.00592-09. Epub 2009 Aug 31.
Ref 555737TMC278, a next-generation nonnucleoside reverse transcriptase inhibitor (NNRTI), active against wild-type and NNRTI-resistant HIV-1. Antimicrob Agents Chemother. 2010 Feb;54(2):718-27. doi: 10.1128/AAC.00986-09. Epub 2009 Nov 23.
Ref 555757Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. J Antimicrob Chemother. 2010 Jul;65(7):1477-85. doi: 10.1093/jac/dkq140. Epub 2010 May 12.
Ref 555773Characterization of genotypic and phenotypic changes in HIV-1-infected patients with virologic failure on an etravirine-containing regimen in the DUET-1 and DUET-2 clinical studies. AIDS Res Hum Retroviruses. 2010 Nov;26(11):1197-205. doi: 10.1089/aid.2009.0302. Epub 2010 Sep 20.
Ref 555809Effect of mutations at position E138 in HIV-1 reverse transcriptase on phenotypic susceptibility and virologic response to etravirine. J Acquir Immune Defic Syndr. 2011 Sep 1;58(1):18-22. doi: 10.1097/QAI.0b013e3182237f74.
Ref 555828Genotypic and phenotypic characterization of HIV-1 isolates obtained from patients on rilpivirine therapy experiencing virologic failure in the phase 3 ECHO and THRIVE studies: 48-week analysis. J Acquir Immune Defic Syndr. 2012 Jan 1;59(1):39-46. doi: 10.1097/QAI.0b013e31823df4da.
Ref 555840Emerging mutations and associated factors in patients displaying treatment failure on an etravirine-containing regimen. Antivir Ther. 2012;17(1):119-23. doi: 10.3851/IMP1886.
Ref 556228The HIVdb system for HIV-1 genotypic resistance interpretation. Intervirology. 2012;55(2):98-101. doi: 10.1159/000331998. Epub 2012 Jan 24.
Ref 555914Quantitative prediction of integrase inhibitor resistance from genotype through consensus linear regression modeling. Virol J. 2013 Jan 3;10:8. doi: 10.1186/1743-422X-10-8.
Ref 555925Significantly improved HIV inhibitor efficacy prediction employing proteochemometric models generated from antivirogram data. PLoS Comput Biol. 2013;9(2):e1002899. doi: 10.1371/journal.pcbi.1002899. Epub 2013 Feb 21.
Ref 555962Non-nucleoside reverse transcriptase inhibitor (NNRTI) cross-resistance: implications for preclinical evaluation of novel NNRTIs and clinical genotypic resistance testing. J Antimicrob Chemother. 2014 Jan;69(1):12-20. doi: 10.1093/jac/dkt316. Epub 2013 Aug 9.
Ref 556038Impact of drug resistance-associated amino acid changes in HIV-1 subtype C on susceptibility to newer nonnucleoside reverse transcriptase inhibitors. Antimicrob Agents Chemother. 2015 Feb;59(2):960-71. doi: 10.1128/AAC.04215-14. Epub 2014 Nov 24.
Ref 556242HIV-1 drug resistance and resistance testing. Infect Genet Evol. 2016 Dec;46:292-307. doi: 10.1016/j.meegid.2016.08.031. Epub 2016 Aug 29.

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