| Drug General Information |
| Drug ID |
D0T6WN
|
| Drug Name |
Rilpivirine |
|
| Synonyms |
500287-72-9; TMC278; Edurant; TMC 278; UNII-FI96A8X663; R278474; TMC-278; 4-{[4-({4-[(E)-2-Cyanoethenyl]-2,6-Dimethylphenyl}amino)pyrimidin-2-Yl]amino}benzonitrile; CHEBI:68606; FI96A8X663; R 278474; 4-{[4-({4-[(E)-2-cyanovinyl]-2,6-dimethylphenyl}amino)pyrimidin-2-yl]amino}benzonitrile; (E)-4-((4-((4-(2-cyanovinyl)-2,6-dimethylphenyl)amino)pyrimidin-2-yl)amino)benzonitrile; (E)-4-(4-(4-(2-cyanovinyl)-2,6-dimethylphenylamino)pyrimidin-2-ylamino)benzonitrile; W-202888; RPV; Mu O-conotoxin |
| Drug Type |
Small molecular drug |
| Structure |
|
| Drug Resistance Mutations |
| Target Name |
HIV Non-Nucleoside reverse transcriptase |
Target Info |
| 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 |
[1] |
| Level of Resistance |
Reduce RPV susceptibility 5 fold |
|
| Mutation info |
Missense: K101P |
[2] |
| Level of Resistance |
Reduce RPV susceptibility >50 fold |
|
| Mutation info |
Missense: L100I |
[3] |
| Level of Resistance |
High-level resistance |
|
| Mutation info |
Missense: Y181C |
[2] |
| Level of Resistance |
Reduce RPV susceptibility about 3 fold |
|
| Mutation info |
Missense: A98G |
[4], [5], [6] |
| Level of Resistance |
Reduce RPV susceptibility about 2-3 fold |
|
| Mutation info |
Missense: E138K |
[7], [8], [9] |
| Level of Resistance |
Reduce RPV susceptibility 2-3 fold |
|
| Mutation info |
Missense: K101E |
[2], [3], [7] |
| Level of Resistance |
Reduce RPV susceptibility about 2 fold |
|
| Mutation info |
Missense: G190E |
[6], [10], [11] |
| Level of Resistance |
Confer high-level resistance to RPV |
|
| Mutation info |
Missense: K238T |
[6], [12], [13] |
| Level of Resistance |
Reduce susceptibility to RPV |
|
| Mutation info |
Missense: G190Q |
[14], [15] |
| Level of Resistance |
Reduce susceptibility to RPV |
|
| Mutation info |
Missense: V179D |
[16], [15] |
| Level of Resistance |
Reduce RPV susceptibility 2-3 fold |
|
| Mutation info |
Missense: L100V |
[17], [6] |
| Level of Resistance |
Reduce susceptibility to RPV |
|
| Mutation info |
Missense: E138G |
[18], [19] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: E138Q |
[18], [19] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: G190A |
[18], [19] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: G190S |
[18], [19] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: H221Y |
[18], [19] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: E138K + M184I |
[18], [20] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: K101E + M184I |
[18], [20] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: K103R + V179D |
[18], [20] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: M230L |
[18], [20] |
| Level of Resistance |
High-level resistance |
|
| Mutation info |
Missense: V179F + Y181C |
[18], [20] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: V179F |
[18], [20] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: V179L |
[18], [20] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: Y181F |
[18], [20] |
| Level of Resistance |
Intermediate resistance |
|
| Mutation info |
Missense: Y181G |
[18], [20] |
| Level of Resistance |
Intermediate resistance |
|
| Mutation info |
Missense: Y181I |
[18], [20] |
| Level of Resistance |
High-level resistance |
|
| Mutation info |
Missense: Y181S |
[18], [20] |
| Level of Resistance |
Intermediate resistance |
|
| Mutation info |
Missense: Y181V |
[18], [20] |
| Level of Resistance |
High-level resistance |
|
| Mutation info |
Missense: Y188F |
[18], [20] |
| Level of Resistance |
Intermediate resistance |
|
| Mutation info |
Missense: E138A |
[8] |
| Level of Resistance |
Reduce RPV susceptibility about 2 fold |
|
| Mutation info |
Missense: E138R |
[21] |
| Level of Resistance |
Reduce RPV susceptibility 2-3 fold |
|
| Mutation info |
Missense: F227C |
[21] |
| Level of Resistance |
Reduce RPV susceptibility 4-5 fold |
|
| Mutation info |
Missense: M230I |
[21] |
| Level of Resistance |
Reduce RPV susceptibility 6 fold |
|
| References |
| REF 1 |
Genotypic 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 2 |
Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. J Antimicrob Chemother. 2010 Jul;65(7):1477-85.
|
| REF 3 |
Human immunodeficiency virus type 1 mutations selected in patients failing efavirenz combination therapy. Antimicrob Agents Chemother. 2000 Sep;44(9):2475-84.
|
| REF 4 |
Distribution of human immunodeficiency virus type 1 protease and reverse transcriptase mutation patterns in 4,183 persons undergoing genotypic resistance testing. Antimicrob Agents Chemother. 2004 Aug;48(8):3122-6.
|
| REF 5 |
A novel nonnucleoside analogue that inhibits human immunodeficiency virus type 1 isolates resistant to current nonnucleoside reverse transcriptase ... Antimicrob Agents Chemother. 2007 Feb;51(2):429-37.
|
| REF 6 |
Significantly improved HIV inhibitor efficacy prediction employing proteochemometric models generated from antivirogram data. PLoS Comput Biol. 2013;9(2):e1002899.
|
| REF 7 |
Characterization 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.
|
| REF 8 |
Effect 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.
|
| REF 9 |
Genotypic 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.
|
| REF 10 |
TMC125 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 11 |
TMC278, 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.
|
| REF 12 |
Human immunodeficiency virus reverse transcriptase and protease sequence database. Nucleic Acids Res. 2003 Jan 1;31(1):298-303.
|
| REF 13 |
The 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 14 |
Amino 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 15 |
Non-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.
|
| REF 16 |
Compilation and prevalence of mutations associated with resistance to non-nucleoside reverse transcriptase inhibitors. Antivir Ther. 2009;14(1):103-9.
|
| REF 17 |
Quantitative prediction of integrase inhibitor resistance from genotype through consensus linear regression modeling. Virol J. 2013 Jan 3;10:8.
|
| REF 18 |
The HIVdb system for HIV-1 genotypic resistance interpretation. Intervirology. 2012;55(2):98-101.
|
| REF 19 |
Current perspectives on HIV-1 antiretroviral drug resistance. Viruses. 2014 Oct 24;6(10):4095-139.
|
| REF 20 |
Global burden of transmitted HIV drug resistance and HIV-exposure categories: a systematic review and meta-analysis. AIDS. 2014 Nov 28;28(18):2751-62.
|
| REF 21 |
Impact 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.
|
