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=NC(NC3=CC=C(C=C3)C#N)=NC(N)=C2Br)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 52 Target ID: CHEMBL4302 Sources: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/000900/WC500034183.pdf	Inhibitor 8228		24.2 µM [IC50]
Human immunodeficiency virus type 1 reverse transcriptase 47 Target ID: CHEMBL247 Sources: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/000900/WC500034183.pdf	Inhibitor 8228		38.4 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
HIV-1 infection 150 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022187lbl.pdf	Primary		Approved 8360	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
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
Report from the XVI International HIV Drug Resistance Workshop.	2007 Aug	17695089
Resistance testing methodologies and mechanisms of resistance.	2007 Dec	18391893
Prevalence of etravirine (TMC-125) resistance mutations in HIV-infected patients with prior experience of non-nucleoside reverse transcriptase inhibitors.	2007 Dec	17913723
TMC125 (etravirine), a second generation non-nucleoside reverse transcriptase inhibitor.	2007 Feb	17763547
Expanded drug access: etravirine (formerly TMC-125).	2007 Jan	17569170
Pharmacokinetics and antiretroviral response to darunavir/ritonavir and etravirine combination in patients with high-level viral resistance.	2007 Jul 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 Jul 7	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 Jul 7	17617270
No patient left behind--better treatments for resistant HIV infection.	2007 Jul 7	17617250
Gateways to clinical trials.	2007 Jul-Aug	17922073
Drug resistant HIV.	2007 Jun 2	17540912
Advances in HIV therapeutics: the 14th CROI.	2007 May	17532664
FDA accepts NDA for priority review of TMC125.	2007 Oct	17992720
Antiviral drugs in the treatment of AIDS: what is in the pipeline ?	2007 Oct 15	17933730
NDA submitted for TMC125.	2007 Sep	17939212
Lessons Learned From 2 Patients With Multidrug-Resistant HIV-1 Infection Successfully Treated With a Darunavir-Containing Antiretroviral Treatment Regimen.	2007 Sep	17641132
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
Highlights of the 15th Conference on Retroviruses and Opportunistic Infections. Advances in antiretroviral therapy.	2008 Apr-May	18441381
Etravirine for the treatment of HIV infection.	2008 Aug	18662109
Follow-up of a multi-drug resistant HIV-1 infected patient successfully treated with darunavir and etravirine.	2008 Aug	18551616
Hemorrhagic cardiomyopathy in male mice treated with an NNRTI: the role of vitamin K.	2008 Feb	18367644
FDA approves new HIV drug after priority review.	2008 Feb	18260807
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
3D-QSAR models on clinically relevant K103N mutant HIV-1 reverse transcriptase obtained from two strategic considerations.	2008 Feb 1	18155520
Etravirine.	2008 Jan	18301801
Gateways to clinical trials.	2008 Jan-Feb	18389098
How developing world concerns need to be part of drug development plans: a case study of four emerging antiretrovirals.	2008 Jul	18598916
New treatment options for HIV salvage patients: an overview of second generation PIs, NNRTIs, integrase inhibitors and CCR5 antagonists.	2008 Jul	18556070
Potential for new antiretrovirals to address unmet needs in the management of HIV-1 infection.	2008 Jun	18479200
Etravirine has no effect on QT and corrected QT interval in HIV-negative volunteers.	2008 Jun	18445705
Etravirine(Intelence) for HIV infection.	2008 Jun 16	18551091
FDA notifications. FDA grants accelerated approval for etravirine.	2008 Mar	18661641
[New drugs for HIV infection].	2008 Mar	18416392
FDA approval: etravirine.	2008 Mar	18399012
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
Complexity of interactions between voriconazole and antiretroviral agents.	2008 May	18413691
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
Is there a role for etravirine in patients with Nonnucleoside reverse transcriptase inhibitor resistance?	2008 May 11	18453859
New drugs: Etravirine, sinecatechins, and desvenlafaxine succinate.	2008 May-Jun	18595832
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
Shifting paradigms: the resistance profile of etravirine.	2008 Oct	18567574
A pharmacokinetic study of etravirine (TMC125) co-administered with ranitidine and omeprazole in HIV-negative volunteers.	2008 Oct	18492125
A survey of the syntheses of active pharmaceutical ingredients for antiretroviral drug combinations critical to access in emerging nations.	2008 Sep	18571246
Evolution of genetic diversity and drug resistance mutations in HIV-1 among untreated patients from Mali between 2005 and 2006.	2008 Sep	18556706

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 `Wed Jul 05 23:24:13 UTC 2023` Edited by `admin` on `Wed Jul 05 23:24:13 UTC 2023`
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

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)