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
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)
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 |
DescriptionCurator'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
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 |
---|---|---|---|
Target ID: CHEMBL4302 |
24.2 µM [IC50] | ||
38.4 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | INTELENCE Approved UseINTELENCE® 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 Date2008 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
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: 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) Sources: Page: p.1Stevens-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) |
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: 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
Title | Date | PubMed |
---|---|---|
Evolution of anti-HIV drug candidates. Part 3: Diarylpyrimidine (DAPY) analogues. | 2001 Sep 3 |
|
One as potent as five. | 2002 Aug 16 |
|
Promising new agents on the horizon. | 2002 Mar |
|
An open-label assessment of TMC 125--a new, next-generation NNRTI, for 7 days in HIV-1 infected individuals with NNRTI resistance. | 2003 Dec 5 |
|
TMC125 exerts similar initial antiviral potency as a five-drug, triple class antiretroviral regimen. | 2003 Dec 5 |
|
A randomized, double-blind, placebo-controlled trial of TMC125 as 7-day monotherapy in antiretroviral naive, HIV-1 infected subjects. | 2003 Nov 21 |
|
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 |
|
TMC125, a novel next-generation nonnucleoside reverse transcriptase inhibitor active against nonnucleoside reverse transcriptase inhibitor-resistant human immunodeficiency virus type 1. | 2004 Dec |
|
TMC-125 Tibotec. | 2004 Feb |
|
TMC 125 possibly effective against NNRTI-resistant HIV. | 2004 Jan |
|
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 |
|
New drugs. | 2005 Jul |
|
Etravirine: R165335, TMC 125, TMC-125, TMC125. | 2006 |
|
Next-generation HIV-1 non-nucleoside reverse transcriptase inhibitors. | 2006 Feb |
|
Drug interactions. Interactions with TMC114 and TMC125. | 2006 Jun-Jul |
|
British HIV Association (BHIVA) guidelines for the treatment of HIV-infected adults with antiretroviral therapy (2006). | 2006 Nov |
|
Potent nonnucleoside reverse transcriptase inhibitors target HIV-1 Gag-Pol. | 2006 Nov |
|
Optimization of pyrimidinyl- and triazinyl-amines as non-nucleoside inhibitors of HIV-1 reverse transcriptase. | 2006 Nov 1 |
|
AIDS 2006 - XVI International Conference. Time to deliver. | 2006 Oct |
|
Antiretroviral treatment of HIV infection: Swedish recommendations 2007. | 2007 |
|
Report from the XVI International HIV Drug Resistance Workshop. | 2007 Aug |
|
Expanded drug access: etravirine (formerly TMC-125). | 2007 Jan |
|
Substrate-dependent inhibition or stimulation of HIV RNase H activity by non-nucleoside reverse transcriptase inhibitors (NNRTIs). | 2007 Jan 12 |
|
Gateways to clinical trials. | 2007 Jan-Feb |
|
Pharmacokinetics and antiretroviral response to darunavir/ritonavir and etravirine combination in patients with high-level viral resistance. | 2007 Jul 11 |
|
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 |
|
No patient left behind--better treatments for resistant HIV infection. | 2007 Jul 7 |
|
Drug resistant HIV. | 2007 Jun 2 |
|
Antiviral drugs in the treatment of AIDS: what is in the pipeline ? | 2007 Oct 15 |
|
Lessons Learned From 2 Patients With Multidrug-Resistant HIV-1 Infection Successfully Treated With a Darunavir-Containing Antiretroviral Treatment Regimen. | 2007 Sep |
|
Hemorrhagic cardiomyopathy in male mice treated with an NNRTI: the role of vitamin K. | 2008 Feb |
|
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 |
|
New treatment options for HIV salvage patients: an overview of second generation PIs, NNRTIs, integrase inhibitors and CCR5 antagonists. | 2008 Jul |
|
48-week data released for etravirine (TMC125). | 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 |
|
Updated prevalence of genotypic resistance among HIV-1 positive patients naïve to antiretroviral therapy: a single center analysis. | 2008 May |
|
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
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/15561844
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
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Record UNII |
0C50HW4FO1
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Record Status |
Validated (UNII)
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Classification Tree | Code System | Code | ||
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EMA ASSESSMENT REPORTS |
INTELENCE (AUTHORIZED: HIV INFECTIONS)
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NCI_THESAURUS |
C97453
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WHO-VATC |
QJ05AG04
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NDF-RT |
N0000175463
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NDF-RT |
N0000009948
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LIVERTOX |
NBK548290
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WHO-ATC |
J05AG04
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NDF-RT |
N0000175460
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m5205
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ETRAVIRINE
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8303
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CHEMBL308954
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C451734
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1266824
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Etravirine
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475969
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63589
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1115
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DB06414
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Related Record | Type | Details | ||
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TARGET -> INHIBITOR | |||
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METABOLIC ENZYME -> SUBSTRATE | |||
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METABOLIC ENZYME -> SUBSTRATE | |||
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METABOLIC ENZYME -> INDUCER | |||
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BINDER->LIGAND |
BINDING
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METABOLIC ENZYME -> INHIBITOR |
ANTAGONIST
IC50
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EXCRETED UNCHANGED |
AMOUNT EXCRETED
FECAL
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TRANSPORTER -> INHIBITOR |
WEAK
IC50
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TRANSPORTER -> SUBSTRATE | |||
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EXCRETED UNCHANGED |
No unchanged drug was recovered in the urine.
URINE
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METABOLIC ENZYME -> SUBSTRATE | |||
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METABOLIC ENZYME -> SUBSTRATE | |||
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METABOLIC ENZYME -> SUBSTRATE |
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PARENT -> METABOLITE | |||
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METABOLITE -> PARENT | |||
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METABOLITE -> PARENT | |||
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PARENT -> METABOLITE | |||
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METABOLITE -> PARENT | |||
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METABOLITE -> PARENT | |||
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METABOLITE -> PARENT |
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IMPURITY -> PARENT |
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ACTIVE MOIETY |
Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Biological Half-life | PHARMACOKINETIC |
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SINGLE DOSE |
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Volume of Distribution | PHARMACOKINETIC |
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Tmax | PHARMACOKINETIC |
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ORAL ADMINISTRATION |
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