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

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

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 49 Target ID: CHEMBL4302 Sources: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/000900/WC500034183.pdf	Inhibitor 7728		24.2 µM [IC50]
Human immunodeficiency virus type 1 reverse transcriptase 45 Target ID: CHEMBL247 Sources: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/000900/WC500034183.pdf	Inhibitor 7728		38.4 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
HIV-1 infection 140 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022187lbl.pdf	Primary		Approved 8043	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

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 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: https://pubmed.ncbi.nlm.nih.gov/17413684 Page: F6	Sources: https://pubmed.ncbi.nlm.nih.gov/17413684 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022187s009lbl.pdf Page: p.5	unhealthy n = 599 Health Status: unhealthy Condition: HIV-1 infection Population Size: 599 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022187s009lbl.pdf Page: p.5	Disc. AE: Rash... AEs leading to discontinuation/dose reduction: Rash (2.2%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022187s009lbl.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022187s009lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: HIV-1 infection Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022187s009lbl.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022187s009lbl.pdf Page: p.1

AEs

AE	Significance	Dose	Population
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 Page: p.5	unhealthy n = 599 Health Status: unhealthy Condition: HIV-1 infection Population Size: 599 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022187s009lbl.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022187s009lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: HIV-1 infection Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022187s009lbl.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022187s009lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: HIV-1 infection Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022187s009lbl.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022187s009lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: HIV-1 infection Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022187s009lbl.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022187s009lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: HIV-1 infection Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022187s009lbl.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022187s009lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: HIV-1 infection Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022187s009lbl.pdf Page: p.1

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
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
eMolecules	31592739	https://www.emolecules.com/cgi-bin/more?vid=31592739

PubMed

Title	Date	PubMed
Researchers explore new anti-HIV agents.	2002 Apr 3	11926873
One as potent as five.	2002 Aug 16	12214591
TMC125 shows promise.	2002 Feb	11892632
Promising new agents on the horizon.	2002 Mar	12141239
Drugs in development.	2002 May	12058698
Validation of a model for the complex of HIV-1 reverse transcriptase with nonnucleoside inhibitor TMC125.	2003 May 21	12785806
A randomized, double-blind, placebo-controlled trial of TMC125 as 7-day monotherapy in antiretroviral naive, HIV-1 infected subjects.	2003 Nov 21	14600520
Current status of the non-nucleoside reverse transcriptase inhibitors of human immunodeficiency virus type 1.	2004	15134549
TMC125: important one-year trial now recruiting in U.S.	2004 Apr 30	15199848
TMC 125 possibly effective against NNRTI-resistant HIV.	2004 Jan	15108674
Effect of stereo and regiochemistry towards wild and multidrug resistant HIV-1 virus: viral potency of chiral PETT derivatives.	2004 May 15	15130770
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	15115397
Gateways to clinical trials.	2005 Jan-Feb	15834459
Etravirine: R165335, TMC 125, TMC-125, TMC125.	2006	17073519
Drug interactions. Interactions with TMC114 and TMC125.	2006 Jun-Jul	17211920
TMC125 study highlights failing NNRTI regimen task.	2006 Nov	17378070
British HIV Association (BHIVA) guidelines for the treatment of HIV-infected adults with antiretroviral therapy (2006).	2006 Nov	17105508
Potent nonnucleoside reverse transcriptase inhibitors target HIV-1 Gag-Pol.	2006 Nov	17096588
The latest in antiretroviral therapy.	2006 Oct	17160151
Anti-HIV agents. Etravirine--interactions with some medications.	2007 Jan	17390478
Anti-HIV agents. The need for etravirine (TMC125).	2007 Jan	17390477
Gateways to clinical trials.	2007 Jan-Feb	17344945
Gateways to clinical trials.	2007 Jul-Aug	17922073
Antiviral drugs in the treatment of AIDS: what is in the pipeline ?	2007 Oct 15	17933730
NDA submitted for TMC125.	2007 Sep	17939212
Prevalence and risk factors for etravirine resistance among patients failing on non-nucleoside reverse transcriptase inhibitors.	2008	18672539
Contraceptive patch: new labeling.	2008 Apr	18377570
Etravirine for the treatment of HIV infection.	2008 Aug	18662109
The incidence of multidrug and full class resistance in HIV-1 infected patients is decreasing over time (2001-2006) in Portugal.	2008 Feb 1	18241328
Etravirine.	2008 Jan	18301801
How developing world concerns need to be part of drug development plans: a case study of four emerging antiretrovirals.	2008 Jul	18598916
FDA notifications. FDA grants accelerated approval for etravirine.	2008 Mar	18661641
48-week data released for etravirine (TMC125).	2008 Mar	18348344
Pharmacokinetic and pharmacodynamic study of the concomitant administration of methadone and TMC125 in HIV-negative volunteers.	2008 Mar	18195053
Successful rescue therapy with Raltegravir (MK-0518) and Etravirine (TMC125) in an hiv-infected patient failing all four classes of antiretroviral drugs.	2008 May	18373415
Updated prevalence of genotypic resistance among HIV-1 positive patients naïve to antiretroviral therapy: a single center analysis.	2008 May	18360912
Adverse cutaneous reactions associated with the newest antiretroviral drugs in patients with human immunodeficiency virus infection.	2008 Nov	18653488
Prevalence of etravirine-associated mutations in clinical samples with resistance to nevirapine and efavirenz.	2008 Nov	18653487

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 `Sat Jun 26 05:19:26 UTC 2021` Edited by `admin` on `Sat Jun 26 05:19:26 UTC 2021`
Record UNII	0C50HW4FO1
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

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

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)