U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C20H15BrN6O
Molecular Weight 435.277
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ETRAVIRINE

SMILES

Cc1cc(cc(C)c1Oc2c(c(N)nc(Nc3ccc(cc3)C#N)n2)Br)C#N

InChI

InChIKey=PYGWGZALEOIKDF-UHFFFAOYSA-N
InChI=1S/C20H15BrN6O/c1-11-7-14(10-23)8-12(2)17(11)28-19-16(21)18(24)26-20(27-19)25-15-5-3-13(9-22)4-6-15/h3-8H,1-2H3,(H3,24,25,26,27)

HIDE SMILES / InChI

Description
Curator's Comment:: description was created based on several sources, including: https://www.drugs.com/ppa/etravirine.html | http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/000900/WC500034183.pdf | http://www.wikidoc.org/index.php/Etravirine

Etravirine (formerly known as TMC125) is an antiretroviral agent more specifically classified as a Non-Nucleoside Reverse Transcriptase Inhibitor. Etravirine exerts its effects via direct inhibition of the reverse transcriptase enzyme of human immunodeficiency virus type 1 (HIV-1). It directly binds reverse transcriptase and consequently blocks DNA-dependent and RNA-dependent polymerase activity. In combination with other antiretroviral agents, it is indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in antiretroviral treatment-experienced adult patients, who have evidence of viral replication and HIV-1 strains resistant to a non-nucleoside reverse transcriptase inhibitor (NNRTI) and other antiretroviral agents. The most common adverse events (incidence > 10%) of any intensity that occurred at a higher rate than placebo are rash and nausea. Etravirine should not be co-administered with the following antiretrovirals: Tipranavir/ritonavir, fosamprenavir/ritonavir, atazanavir/ritonavir; Protease inhibitors administered without ritonavir; NNRTIs.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
INTELENCE

Approved Use

INTELENCE® Registered trademark of Tibotec Pharmaceuticals, in combination with other antiretroviral agents, is indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in antiretroviral treatment-experienced adult patients, who have evidence of viral replication and HIV-1 strains resistant to a non-nucleoside reverse transcriptase inhibitor (NNRTI) and other antiretroviral agents. This indication is based on Week 48 analyses from 2 randomized, double-blind, placebo-controlled trials of INTELENCE®. Both studies were conducted in clinically advanced, 3-class antiretroviral (NNRTI, N[t

Launch Date

1.20061441E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
296.74 ng/mL
200 mg 2 times / day steady-state, oral
dose: 200 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: DARUNAVIR
ETRAVIRINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
4531.53 ng × h/mL
200 mg 2 times / day steady-state, oral
dose: 200 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: DARUNAVIR
ETRAVIRINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
41 h
200 mg 2 times / day steady-state, oral
dose: 200 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: DARUNAVIR
ETRAVIRINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
0.1%
200 mg 2 times / day steady-state, oral
dose: 200 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: DARUNAVIR
ETRAVIRINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
Doses

Doses

DosePopulationAdverse events​
800 mg 2 times / day multiple, oral
Highest studied dose
Dose: 800 mg, 2 times / day
Route: oral
Route: multiple
Dose: 800 mg, 2 times / day
Sources: Page: F6
unhealthy, 29–63
n = 79
Health Status: unhealthy
Condition: HIV-1 infection
Age Group: 29–63
Sex: M+F
Population Size: 79
Sources: Page: F6
200 mg 2 times / day multiple, oral
Recommended
Dose: 200 mg, 2 times / day
Route: oral
Route: multiple
Dose: 200 mg, 2 times / day
Sources: Page: p.5
unhealthy
n = 599
Health Status: unhealthy
Condition: HIV-1 infection
Population Size: 599
Sources: Page: p.5
Disc. AE: Rash...
AEs leading to
discontinuation/dose reduction:
Rash (2.2%)
Sources: Page: p.5
200 mg 2 times / day multiple, oral
Recommended
Dose: 200 mg, 2 times / day
Route: oral
Route: multiple
Dose: 200 mg, 2 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: HIV-1 infection
Sources: Page: p.1
Disc. AE: Reaction skin, Stevens-Johnson syndrome...
AEs leading to
discontinuation/dose reduction:
Reaction skin (severe|grade 4|grade 5)
Stevens-Johnson syndrome (severe|grade 4|grade 5)
Hypersensitivity reaction (severe|grade 4|grade 5)
Toxic epidermal necrolysis (severe|grade 4|grade 5)
Erythema multiforme (severe|grade 4|grade 5)
Sources: Page: p.1
AEs

AEs

AESignificanceDosePopulation
Rash 2.2%
Disc. AE
200 mg 2 times / day multiple, oral
Recommended
Dose: 200 mg, 2 times / day
Route: oral
Route: multiple
Dose: 200 mg, 2 times / day
Sources: Page: p.5
unhealthy
n = 599
Health Status: unhealthy
Condition: HIV-1 infection
Population Size: 599
Sources: Page: p.5
Erythema multiforme severe|grade 4|grade 5
Disc. AE
200 mg 2 times / day multiple, oral
Recommended
Dose: 200 mg, 2 times / day
Route: oral
Route: multiple
Dose: 200 mg, 2 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: HIV-1 infection
Sources: Page: p.1
Hypersensitivity reaction severe|grade 4|grade 5
Disc. AE
200 mg 2 times / day multiple, oral
Recommended
Dose: 200 mg, 2 times / day
Route: oral
Route: multiple
Dose: 200 mg, 2 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: HIV-1 infection
Sources: Page: p.1
Reaction skin severe|grade 4|grade 5
Disc. AE
200 mg 2 times / day multiple, oral
Recommended
Dose: 200 mg, 2 times / day
Route: oral
Route: multiple
Dose: 200 mg, 2 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: HIV-1 infection
Sources: Page: p.1
Stevens-Johnson syndrome severe|grade 4|grade 5
Disc. AE
200 mg 2 times / day multiple, oral
Recommended
Dose: 200 mg, 2 times / day
Route: oral
Route: multiple
Dose: 200 mg, 2 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: HIV-1 infection
Sources: Page: p.1
Toxic epidermal necrolysis severe|grade 4|grade 5
Disc. AE
200 mg 2 times / day multiple, oral
Recommended
Dose: 200 mg, 2 times / day
Route: oral
Route: multiple
Dose: 200 mg, 2 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: HIV-1 infection
Sources: Page: p.1
PubMed

PubMed

TitleDatePubMed
Correlations between factors determining the pharmacokinetics and antiviral activity of HIV-1 non-nucleoside reverse transcriptase inhibitors of the diaryltriazine and diarylpyrimidine classes of compounds.
2004
Recent advances in the development of next generation non-nucleoside reverse transcriptase inhibitors.
2004
TMC125: important one-year trial now recruiting in U.S.
2004 Apr 30
Effect of stereo and regiochemistry towards wild and multidrug resistant HIV-1 virus: viral potency of chiral PETT derivatives.
2004 May 15
Roles of conformational and positional adaptability in structure-based design of TMC125-R165335 (etravirine) and related non-nucleoside reverse transcriptase inhibitors that are highly potent and effective against wild-type and drug-resistant HIV-1 variants.
2004 May 6
A series of diaryltriazines and diarylpyrimidines are highly potent nonnucleoside reverse transcriptase inhibitors with possible applications as microbicides.
2004 Oct
New non-nucleoside reverse transcriptase inhibitors (NNRTIs) in development for the treatment of HIV infections.
2004 Oct
HIV-chemotherapy and -prophylaxis: new drugs, leads and approaches.
2004 Sep
New drugs.
2005 Jul
Crystallography and the design of anti-AIDS drugs: conformational flexibility and positional adaptability are important in the design of non-nucleoside HIV-1 reverse transcriptase inhibitors.
2005 Jun
Emerging anti-HIV drugs.
2005 May
The molecular basis of resilience to the effect of the Lys103Asn mutation in non-nucleoside HIV-1 reverse transcriptase inhibitors studied by targeted molecular dynamics simulations.
2005 May 25
TMC125: new results, large phase III trial begins.
2005 Oct-Nov
Report from the 13th retrovirus conference. New data on TMC114 and TMC125.
2006 Apr
Optimization of diarylamines as non-nucleoside inhibitors of HIV-1 reverse transcriptase.
2006 Feb
The clinical pharmacology of antiretrovirals in development.
2006 Jun
British HIV Association (BHIVA) guidelines for the treatment of HIV-infected adults with antiretroviral therapy (2006).
2006 Nov
Pharmacokinetics of darunavir/ritonavir and TMC125 alone and coadministered in HIV-negative volunteers.
2007
Antiretroviral treatment of HIV infection: Swedish recommendations 2007.
2007
Prevalence of etravirine (TMC-125) resistance mutations in HIV-infected patients with prior experience of non-nucleoside reverse transcriptase inhibitors.
2007 Dec
TMC125 (etravirine), a second generation non-nucleoside reverse transcriptase inhibitor.
2007 Feb
Expanded drug access: etravirine (formerly TMC-125).
2007 Jan
Anti-HIV agents. Brain side effects not common with etravirine.
2007 Jan
Anti-HIV agents. Effectiveness of etravirine in treatment-experienced PHAs.
2007 Jan
Anti-HIV agents. Etravirine--interactions with some medications.
2007 Jan
Anti-HIV agents. The need for etravirine (TMC125).
2007 Jan
Gateways to clinical trials.
2007 Jan-Feb
Gateways to clinical trials.
2007 Jul-Aug
Drug resistant HIV.
2007 Jun 2
Efficacy and safety of etravirine (TMC125) in patients with highly resistant HIV-1: primary 24-week analysis.
2007 Mar 30
Modelling-based prediction of clinical benefits from etravirine in the TMC125-C223 trial.
2007 Mar-Apr
Advances in HIV therapeutics: the 14th CROI.
2007 May
FDA accepts NDA for priority review of TMC125.
2007 Oct
Antiviral drugs in the treatment of AIDS: what is in the pipeline ?
2007 Oct 15
NDA submitted for TMC125.
2007 Sep
Highlights of the 15th Conference on Retroviruses and Opportunistic Infections. Advances in antiretroviral therapy.
2008 Apr-May
Follow-up of a multi-drug resistant HIV-1 infected patient successfully treated with darunavir and etravirine.
2008 Aug
FDA approves new HIV drug after priority review.
2008 Feb
The incidence of multidrug and full class resistance in HIV-1 infected patients is decreasing over time (2001-2006) in Portugal.
2008 Feb 1
3D-QSAR models on clinically relevant K103N mutant HIV-1 reverse transcriptase obtained from two strategic considerations.
2008 Feb 1
How developing world concerns need to be part of drug development plans: a case study of four emerging antiretrovirals.
2008 Jul
New treatment options for HIV salvage patients: an overview of second generation PIs, NNRTIs, integrase inhibitors and CCR5 antagonists.
2008 Jul
Potential for new antiretrovirals to address unmet needs in the management of HIV-1 infection.
2008 Jun
FDA approval: etravirine.
2008 Mar
Pharmacokinetic and pharmacodynamic study of the concomitant administration of methadone and TMC125 in HIV-negative volunteers.
2008 Mar
Successful rescue therapy with Raltegravir (MK-0518) and Etravirine (TMC125) in an hiv-infected patient failing all four classes of antiretroviral drugs.
2008 May
Is there a role for etravirine in patients with Nonnucleoside reverse transcriptase inhibitor resistance?
2008 May 11
Shifting paradigms: the resistance profile of etravirine.
2008 Oct
A survey of the syntheses of active pharmaceutical ingredients for antiretroviral drug combinations critical to access in emerging nations.
2008 Sep
Evolution of genetic diversity and drug resistance mutations in HIV-1 among untreated patients from Mali between 2005 and 2006.
2008 Sep
Patents

Sample Use Guides

200 mg (two 100 mg tablets) taken twice daily following a meal
Route of Administration: Oral
TMC125, was highly active against wild-type HIV-1 (50% effective concentration [EC50] = 1.4 to 4.8 nM) and showed some activity against HIV-2 (EC50 = 3.5 microM). TMC125 also inhibited a series of HIV-1 group M subtypes and circulating recombinant forms and a group O virus.
Name Type Language
ETRAVIRINE
DASH   EMA EPAR   INN   JAN   MART.   MI   ORANGE BOOK   USAN   VANDF   WHO-DD  
USAN   INN  
Official Name English
ETRAVIRINE [JAN]
Common Name English
ETRAVIRINE [INN]
Common Name English
TMC 125
Code English
ETRAVIRINE [MI]
Common Name English
ETRAVIRINE [MART.]
Common Name English
INTELENCE
Brand Name English
ETRAVIRINE [VANDF]
Common Name English
R165335
Code English
ETRAVIRINE [WHO-DD]
Common Name English
BENZONITRILE, 4-((6-AMINO-5-BROMO-2-((4-CYANOPHENYL)AMINO)-4-PYRIMIDINYL)OXY)-3,5-DIMETHYL-
Systematic Name English
4-((6-AMINO-5-BROMO-2-((4-CYANOPHENYL)AMINO)-4-PYRIMIDINYL)OXY)-3,5-DIMETHYL-BENZONITRILE
Systematic Name English
TMC125
Code English
ETRAVIRINE [USAN]
Common Name English
TMC-125
Code English
ETRAVIRINE [EMA EPAR]
Common Name English
ETRAVIRINE [ORANGE BOOK]
Common Name English
R-165335
Code English
Classification Tree Code System Code
EMA ASSESSMENT REPORTS INTELENCE (AUTHORIZED: HIV INFECTIONS)
Created by admin on Sat Jun 26 05:19:26 UTC 2021 , Edited by admin on Sat Jun 26 05:19:26 UTC 2021
NCI_THESAURUS C97453
Created by admin on Sat Jun 26 05:19:26 UTC 2021 , Edited by admin on Sat Jun 26 05:19:26 UTC 2021
WHO-VATC QJ05AG04
Created by admin on Sat Jun 26 05:19:26 UTC 2021 , Edited by admin on Sat Jun 26 05:19:26 UTC 2021
NDF-RT N0000175463
Created by admin on Sat Jun 26 05:19:26 UTC 2021 , Edited by admin on Sat Jun 26 05:19:26 UTC 2021
NDF-RT N0000009948
Created by admin on Sat Jun 26 05:19:26 UTC 2021 , Edited by admin on Sat Jun 26 05:19:26 UTC 2021
LIVERTOX 390
Created by admin on Sat Jun 26 05:19:26 UTC 2021 , Edited by admin on Sat Jun 26 05:19:26 UTC 2021
WHO-ATC J05AG04
Created by admin on Sat Jun 26 05:19:26 UTC 2021 , Edited by admin on Sat Jun 26 05:19:26 UTC 2021
NDF-RT N0000175460
Created by admin on Sat Jun 26 05:19:26 UTC 2021 , Edited by admin on Sat Jun 26 05:19:26 UTC 2021
Code System Code Type Description
PUBCHEM
193962
Created by admin on Sat Jun 26 05:19:26 UTC 2021 , Edited by admin on Sat Jun 26 05:19:26 UTC 2021
PRIMARY
EPA CompTox
269055-15-4
Created by admin on Sat Jun 26 05:19:26 UTC 2021 , Edited by admin on Sat Jun 26 05:19:26 UTC 2021
PRIMARY
MERCK INDEX
M5205
Created by admin on Sat Jun 26 05:19:26 UTC 2021 , Edited by admin on Sat Jun 26 05:19:26 UTC 2021
PRIMARY Merck Index
WIKIPEDIA
ETRAVIRINE
Created by admin on Sat Jun 26 05:19:26 UTC 2021 , Edited by admin on Sat Jun 26 05:19:26 UTC 2021
PRIMARY
CAS
269055-15-4
Created by admin on Sat Jun 26 05:19:26 UTC 2021 , Edited by admin on Sat Jun 26 05:19:26 UTC 2021
PRIMARY
INN
8303
Created by admin on Sat Jun 26 05:19:26 UTC 2021 , Edited by admin on Sat Jun 26 05:19:26 UTC 2021
PRIMARY
ChEMBL
CHEMBL308954
Created by admin on Sat Jun 26 05:19:26 UTC 2021 , Edited by admin on Sat Jun 26 05:19:26 UTC 2021
PRIMARY
MESH
C451734
Created by admin on Sat Jun 26 05:19:26 UTC 2021 , Edited by admin on Sat Jun 26 05:19:26 UTC 2021
PRIMARY
NCI_THESAURUS
C73195
Created by admin on Sat Jun 26 05:19:26 UTC 2021 , Edited by admin on Sat Jun 26 05:19:26 UTC 2021
PRIMARY
EVMPD
SUB25650
Created by admin on Sat Jun 26 05:19:26 UTC 2021 , Edited by admin on Sat Jun 26 05:19:26 UTC 2021
PRIMARY
FDA UNII
0C50HW4FO1
Created by admin on Sat Jun 26 05:19:26 UTC 2021 , Edited by admin on Sat Jun 26 05:19:26 UTC 2021
PRIMARY
LACTMED
Etravirine
Created by admin on Sat Jun 26 05:19:26 UTC 2021 , Edited by admin on Sat Jun 26 05:19:26 UTC 2021
PRIMARY
RXCUI
475969
Created by admin on Sat Jun 26 05:19:26 UTC 2021 , Edited by admin on Sat Jun 26 05:19:26 UTC 2021
PRIMARY RxNorm
DRUG CENTRAL
1115
Created by admin on Sat Jun 26 05:19:26 UTC 2021 , Edited by admin on Sat Jun 26 05:19:26 UTC 2021
PRIMARY
DRUG BANK
DB06414
Created by admin on Sat Jun 26 05:19:26 UTC 2021 , Edited by admin on Sat Jun 26 05:19:26 UTC 2021
PRIMARY