ETRAVIRINE

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 Search

SMILES

CC1=CC(=CC(C)=C1OC2=C(Br)C(N)=NC(NC3=CC=C(C=C3)C#N)=N2)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

Molecular Formula	C20H15BrN6O
Molecular Weight	435.277
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022187lbl.pdf
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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
P-glycoprotein 1 54 Target ID: CHEMBL4302 Sources: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/000900/WC500034183.pdf	Inhibitor 8504		24.2 µM [IC50]
Human immunodeficiency virus type 1 reverse transcriptase 70 Target ID: CHEMBL247 Sources: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/000900/WC500034183.pdf	Inhibitor 8504		38.4 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
HIV-1 infection 156 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022187lbl.pdf	Primary		Approved 8583	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 2008

C_max

Value	Dose	Co-administered	Analyte	Population
296.74 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022187lbl.pdf	200 mg 2 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered: DARUNAVIR	DARUNAVIR	ETRAVIRINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED

AUC

Value	Dose	Co-administered	Analyte	Population
4531.53 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022187lbl.pdf	200 mg 2 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered: DARUNAVIR	DARUNAVIR	ETRAVIRINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED

T_1/2

Value	Dose	Co-administered	Analyte	Population
41 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022187lbl.pdf	200 mg 2 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered: DARUNAVIR	DARUNAVIR	ETRAVIRINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED

F_unbound

Value	Dose	Co-administered	Analyte	Population
0.1% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022187lbl.pdf	200 mg 2 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered: DARUNAVIR	DARUNAVIR	ETRAVIRINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED

Doses

Dose	Population	Adverse 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: https://pubmed.ncbi.nlm.nih.gov/17413684	unhealthy, 29–63 Health Status: unhealthy Age Group: 29–63 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/17413684	Sources: https://pubmed.ncbi.nlm.nih.gov/17413684
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022187s009lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022187s009lbl.pdf	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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022187s009lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022187s009lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022187s009lbl.pdf	Disc. AE: Rash... AEs leading to discontinuation/dose reduction: Rash (2.2%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022187s009lbl.pdf

AEs

AE	Significance	Dose	Population
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022187s009lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022187s009lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022187s009lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022187s009lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022187s009lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022187s009lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022187s009lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022187s009lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022187s009lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022187s009lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022187s009lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022187s009lbl.pdf

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:63589	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:63589
ChemicalBook	CB51509336	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB51509336
eMolecules	31592739	https://www.emolecules.com/cgi-bin/more?vid=31592739
MolPort	MolPort-009-194-145	https://www.molport.com/shop/molecule-link/MolPort-009-194-145
Selleck Chemicals	etravirine-tmc125	http://www.selleckchem.com/products/etravirine-tmc125.html
ZINC	ZINC000000602632	http://zinc15.docking.org/substances/ZINC000000602632

PubMed

Title	Date	PubMed
Adverse cutaneous reactions associated with the newest antiretroviral drugs in patients with human immunodeficiency virus infection.	2008-11	18653488
Prevalence of etravirine-associated mutations in clinical samples with resistance to nevirapine and efavirenz.	2008-11	18653487
Shifting paradigms: the resistance profile of etravirine.	2008-10	18567574
A pharmacokinetic study of etravirine (TMC125) co-administered with ranitidine and omeprazole in HIV-negative volunteers.	2008-10	18492125
A survey of the syntheses of active pharmaceutical ingredients for antiretroviral drug combinations critical to access in emerging nations.	2008-09	18571246
Evolution of genetic diversity and drug resistance mutations in HIV-1 among untreated patients from Mali between 2005 and 2006.	2008-09	18556706
Etravirine for the treatment of HIV infection.	2008-08	18662109
Follow-up of a multi-drug resistant HIV-1 infected patient successfully treated with darunavir and etravirine.	2008-08	18551616
New drugs: Etravirine, sinecatechins, and desvenlafaxine succinate.	2008-07-04	18595832
How developing world concerns need to be part of drug development plans: a case study of four emerging antiretrovirals.	2008-07	18598916
New treatment options for HIV salvage patients: an overview of second generation PIs, NNRTIs, integrase inhibitors and CCR5 antagonists.	2008-07	18556070
Etravirine(Intelence) for HIV infection.	2008-06-16	18551091
Potential for new antiretrovirals to address unmet needs in the management of HIV-1 infection.	2008-06	18479200
Etravirine has no effect on QT and corrected QT interval in HIV-negative volunteers.	2008-06	18445705
Is there a role for etravirine in patients with Nonnucleoside reverse transcriptase inhibitor resistance?	2008-05-11	18453859
Complexity of interactions between voriconazole and antiretroviral agents.	2008-05	18413691
Successful rescue therapy with Raltegravir (MK-0518) and Etravirine (TMC125) in an hiv-infected patient failing all four classes of antiretroviral drugs.	2008-05	18373415
Updated prevalence of genotypic resistance among HIV-1 positive patients naïve to antiretroviral therapy: a single center analysis.	2008-05	18360912
Highlights of the 15th Conference on Retroviruses and Opportunistic Infections. Advances in antiretroviral therapy.	2008-04-29	18441381
Gateways to clinical trials.	2008-04-05	18389098
Contraceptive patch: new labeling.	2008-04	18377570
FDA notifications. FDA grants accelerated approval for etravirine.	2008-03	18661641
[New drugs for HIV infection].	2008-03	18416392
FDA approval: etravirine.	2008-03	18399012
48-week data released for etravirine (TMC125).	2008-03	18348344
Pharmacokinetic and pharmacodynamic study of the concomitant administration of methadone and TMC125 in HIV-negative volunteers.	2008-03	18195053
The incidence of multidrug and full class resistance in HIV-1 infected patients is decreasing over time (2001-2006) in Portugal.	2008-02-01	18241328
3D-QSAR models on clinically relevant K103N mutant HIV-1 reverse transcriptase obtained from two strategic considerations.	2008-02-01	18155520
Hemorrhagic cardiomyopathy in male mice treated with an NNRTI: the role of vitamin K.	2008-02	18367644
FDA approves new HIV drug after priority review.	2008-02	18260807
Etravirine.	2008-01	18301801
Prevalence and risk factors for etravirine resistance among patients failing on non-nucleoside reverse transcriptase inhibitors.	2008	18672539
Resistance testing methodologies and mechanisms of resistance.	2007-12	18391893
Prevalence of etravirine (TMC-125) resistance mutations in HIV-infected patients with prior experience of non-nucleoside reverse transcriptase inhibitors.	2007-12	17913723
Antiviral drugs in the treatment of AIDS: what is in the pipeline ?	2007-10-15	17933730
Gateways to clinical trials.	2007-10-09	17922073
FDA accepts NDA for priority review of TMC125.	2007-10	17992720
NDA submitted for TMC125.	2007-09	17939212
Lessons Learned From 2 Patients With Multidrug-Resistant HIV-1 Infection Successfully Treated With a Darunavir-Containing Antiretroviral Treatment Regimen.	2007-09	17641132
Report from the XVI International HIV Drug Resistance Workshop.	2007-08	17695089
Pharmacokinetics and antiretroviral response to darunavir/ritonavir and etravirine combination in patients with high-level viral resistance.	2007-07-11	17589191
Efficacy and safety of TMC125 (etravirine) in treatment-experienced HIV-1-infected patients in DUET-2: 24-week results from a randomised, double-blind, placebo-controlled trial.	2007-07-07	17617271
Efficacy and safety of TMC125 (etravirine) in treatment-experienced HIV-1-infected patients in DUET-1: 24-week results from a randomised, double-blind, placebo-controlled trial.	2007-07-07	17617270
No patient left behind--better treatments for resistant HIV infection.	2007-07-07	17617250
Drug resistant HIV.	2007-06-02	17540912
Advances in HIV therapeutics: the 14th CROI.	2007-05	17532664
TMC125 (etravirine), a second generation non-nucleoside reverse transcriptase inhibitor.	2007-02	17763547
Expanded drug access: etravirine (formerly TMC-125).	2007-01	17569170
Pharmacokinetics of darunavir/ritonavir and TMC125 alone and coadministered in HIV-negative volunteers.	2007	17713162
Antiretroviral treatment of HIV infection: Swedish recommendations 2007.	2007	17577810

Patents

Sample Use Guides

In Vivo Use Guide

200 mg (two 100 mg tablets) taken twice daily following a meal

Route of Administration: Oral

In Vitro Use Guide

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.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:13:38 GMT 2025` Edited by `admin` on `Mon Mar 31 18:13:38 GMT 2025`
Record UNII	0C50HW4FO1
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

INTELENCE

Preferred Name

English

ETRAVIRINE

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

ETRAVIRINE [VANDF]

Common Name

English

Etravirine [WHO-DD]

Common Name

English

R165335

Code

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)