Etravirine

Summary

Etravirine (CHEMBL308954) is an approved small-molecule HIV-1 reverse transcriptase inhibitor (ATC J05AG04); indicated across 6 conditions including hiv infectious disease and viral infectious disease.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: J05AG04
• Indications: 6 conditions
• Clinical trials: 47
• Chemistry: 435.3 Da · C20H15BrN6O

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL308954
Name	Etravirine
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	193962
ChEBI	CHEBI:63589
ATC	J05AG04
Molecular formula	C20H15BrN6O
Molecular weight	435.3
InChIKey	PYGWGZALEOIKDF-UHFFFAOYSA-N

SMILES: CC1=CC(=CC(=C1OC2=NC(=NC(=C2Br)N)NC3=CC=C(C=C3)C#N)C)C#N

IUPAC name: 4-[6-amino-5-bromo-2-(4-cyanoanilino)pyrimidin-4-yl]oxy-3,5-dimethylbenzonitrile

ChEBI definition: An aminopyrimidine that consists of 2,6-diaminopyrimidine bearing a bromo substituent at position 5, a 4-cyano-2,6-dimethylphenoxy substituent at position 4 and having a 4-cyanophenyl substituent attached to the 2-amino group. NNRTI of HIV-1, binds directly to RT and blocks RNA-dependent and DNA-dependent DNA polymerase activities

Pharmacological roles (ChEBI): HIV-1 reverse transcriptase inhibitor, antiviral agent.

Also known as: Etravirina, Etravirine, Intelence, R-165335, R165335, TMC 125, TMC-125, TMC125, etravirine, ETRAVIRINE, Etravirin, ETRAVIRINE (TMC125)

Patent coverage: 2,863 distinct patent families (11,287 SureChEMBL compound mentions), from 1 matched compound structure(s). Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Broader ChEMBL bioactivity targets: 22 (assay-derived). Sample: Alpha-2A adrenergic receptor, D(1A) dopamine receptor, Estrogen receptor, Progesterone receptor, Muscarinic acetylcholine receptor M2, Muscarinic acetylcholine receptor M1, Prostaglandin G/H synthase 1, Sodium-dependent noradrenaline transporter, Adenosine receptor A1, Mu-type opioid receptor.

Bioactivity

ChEMBL activities: 24 potent at pChembl ≥ 5 of 39 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
PGR	7.1	AC50	80	nM	CHEMBL_ACT_25204077
CYP2C9	6.56	IC50	277	nM	CHEMBL_ACT_25508205
CYP2C9	6.56	IC50	277	nM	CHEMBL_ACT_26142473
CYP2C9	6.56	IC50	277	nM	CHEMBL_ACT_29097763
CYP2C9	6.55	IC50	280	nM	CHEMBL_ACT_29257276
CYP2C19	6.3	IC50	496	nM	CHEMBL_ACT_25508209
CYP2C19	6.3	IC50	496	nM	CHEMBL_ACT_26142477
CYP2C19	6.3	IC50	496	nM	CHEMBL_ACT_29097771
CYP2C19	6.3	IC50	500	nM	CHEMBL_ACT_29257279
CHRM1	5.57	AC50	2710	nM	CHEMBL_ACT_25210027
P25779	5.4	IC50	4000	nM	CHEMBL_ACT_3307705
DRD1	5.34	AC50	4530	nM	CHEMBL_ACT_25114996
ABCC3	5.29	IC50	5100	nM	CHEMBL_ACT_5308713
SLC6A2	5.23	AC50	5880	nM	CHEMBL_ACT_25145786
ABCG2	5.22	IC50	6000	nM	CHEMBL_ACT_5308712
ESR1	5.2	AC50	6280	nM	CHEMBL_ACT_25138644
KCNH2	5.13	AC50	7320	nM	CHEMBL_ACT_25117234
CYP1A2	5.13	IC50	7480	nM	CHEMBL_ACT_25508201
CYP1A2	5.13	IC50	7480	nM	CHEMBL_ACT_26142469
CYP1A2	5.13	IC50	7480	nM	CHEMBL_ACT_29097755
CYP1A2	5.13	IC50	7480	nM	CHEMBL_ACT_29257271
ABCB1	5.12	IC50	7600	nM	CHEMBL_ACT_5308708
ABCC2	5.11	IC50	7800	nM	CHEMBL_ACT_5308709
ABCC1	5.07	IC50	8500	nM	CHEMBL_ACT_5308710

Target pathways

No target-pathway data for this drug (no mapped target genes).

Indications & clinical

Indications

6 indications (3 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
HIV infectious disease	4	MONDO:0005109	EFO:0000180
viral infectious disease	4	MONDO:0005108	EFO:0000763
AIDS	2	MONDO:0012268	EFO:0000765
Friedreich ataxia	2	MONDO:0100339	MONDO:0100339

2 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 47.

Phase distribution

Phase	Trials
PHASE2	14
PHASE1	11
PHASE3	9
PHASE4	7
Not specified	5
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00782301	PHASE4	WITHDRAWN	Maraviroc Versus Etravirine In Combination With Antiretroviral Therapy In Drug Experienced HIV And Hepatitis Co-Infected Patients
NCT00855413	PHASE4	TERMINATED	HIV Viremia and Persistence in Acutely HIV-Infected Patients Treated With Darunavir/Ritonavir and Etravirine
NCT01045369	PHASE4	COMPLETED	A Pilot Study of Kaletra and Intelence Tablets in Naive Subjects
NCT01118871	PHASE4	TERMINATED	The First Failure Study
NCT01121809	PHASE4	COMPLETED	Plasma and Intracellular Concentrations of Raltegravir and Etravirine Administered Once Daily
NCT01422330	PHASE4	COMPLETED	A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Etravirine Administered in Combination With Other Antiretroviral Agents in Antiretroviral Treatment-Experienced HIV-1 Infected Patients
NCT01641367	PHASE4	COMPLETED	A5288/MULTI-OCTAVE: Management Using Latest Technologies to Optimize Combination Therapy After Viral Failure
NCT00254046	PHASE3	COMPLETED	TMC125-C206: A Phase III Study to Investigate the Efficacy, Tolerability and Safety of TMC125 as Part of an Antiretroviral Regimen, Including TMC114/Ritonavir and an Investigator-selected Optimized Background, in HIV-1 Infected Patients With Limited to no Treatment Options.
NCT00255099	PHASE3	COMPLETED	TMC125-C216: A Phase III Study to Investigate the Efficacy, Tolerability and Safety of TMC125 as Part of an Antiretroviral Regimen, Including TMC114/Ritonavir and an Investigator-selected Optimized Background, in HIV-1 Infected Patients With Limited to no Treatment Options.
NCT00354627	PHASE3	COMPLETED	The TMC125-C214 Study Provides Early Access to TMC125 for HIV-1 Infected Patients Who Have Failed Multiple Antiretroviral Regimens and Will Also Gather Information on the Long-term Safety and Tolerability of TMC125 Combined With Other Antiretroviral Drugs
NCT00359021	PHASE3	COMPLETED	An Open-label Trial With TMC125 in Patients Who Have Virologically Failed in a DUET Trial (TMC125-C206 or TMC125-C216).
NCT00460746	PHASE3	COMPLETED	Enfuvirtide/Current Protease Inhibitor Switch to PREZISTA (Darunavir)/Ritonavir + TMC125 in HIV Patients With Enfuvirtide Side Effects.
NCT00537394	PHASE3	COMPLETED	Optimizing Treatment for Treatment-Experienced, HIV-Infected People
NCT00792324	PHASE3	COMPLETED	Pilot Study Switching Individuals Receiving EFV With Continuing Central Nervous System Toxicity to TMC125
NCT00855335	PHASE3	COMPLETED	A Single-arm, Open-label, Study to Assess the Pharmacokinetics of Darunavir and Ritonavir, Darunavir and Cobicistat, Etravirine, and Rilpivirine in HIV-1 Infected Pregnant Women
NCT00980538	PHASE3	COMPLETED	TMC125-TiDP35-C239 - Continued Access to Etravirine (ETR) in Treatment Experienced HIV-1 Infected Participants
NCT00081978	PHASE2	COMPLETED	TMC125-C223: TMC125 in HIV-1 Infected Subjects
NCT00111280	PHASE2	COMPLETED	TMC125-C211: Trial of TMC125 in HIV-1 Infected Subjects Who Were in a Sponsor Selected TMC125 Trial
NCT00128830	PHASE2	COMPLETED	A Study With TMC125 in Human Immunodeficiency Virus (HIV) Type 1 Infected Patients, Who Were Treated With TMC125 Arm in a Sponsor-Selected TMC125 Study
NCT00225303	PHASE2	COMPLETED	TMC125-C227: A Phase II Randomized, Active-Controlled, Open Label Trial to Investigate the Efficacy and Tolerability of TMC125 in HIV-1 Infected Subjects, Who Are PI-Naive and With Documented Genotypic Evidence of NNRTI Resistance From Previous NNRTI Use
NCT00412646	PHASE2	COMPLETED	TMC125-C203: Phase II Randomized (Patients Are Assigned Different Treatments Based on Chance), Placebo Controlled Dose Escalating Trial of TMC125 in HIV-1 Infected Patients
NCT00460382	PHASE2	COMPLETED	Clinical Trial to Assess the Efficacy of Darunavir/Ritonavir (DRV/r), Etravirine (ETV) and Raltegravir (MK-0518) in HIV Patients With Resistant Viruses
NCT00665847	PHASE2	COMPLETED	TMC125-TiDP35-C213: Safety and Antiviral Activity of Etravirine (TMC125) in Treatment-Experienced, HIV Infected Children and Adolescents
NCT00823979	PHASE2	TERMINATED	A Phase 2B Multicenter, Randomized, Comparative Trial Of UK-453,061 Versus Etravirine In Combination With Darunavir/Ritonavir And A Nucleos(t)Ide Reverse Transcriptase Inhibitor For The Treatment Of Antiretroviral Experienced HIV-1 Infected Subjects With Evidence Of NNRTI Resistant HIV-1
NCT00959894	PHASE2	COMPLETED	Evaluating Once Daily Etravirine in Treatment-Naive Adults With HIV Infection
NCT01199731	PHASE2	TERMINATED	Dose-finding Study of GSK2248761 in Antiretroviral Therapy-experienced Subjects With NNRTI-resistant HIV Infection
NCT01199939	PHASE2	COMPLETED	A Study of the Once Daily Combination of Etravirine and Darunavir/Ritonavir As Dual Therapy in Early Treatment-Experienced Patients
NCT01254656	PHASE2	TERMINATED	A Long Term Safety Study Of Lersivirine For The Treatment Of HIV-1 Infection In Subjects Who Have Completed Treatment With Lersivirine In Studies A5271015 And A5271022
NCT01504841	PHASE1/PHASE2	COMPLETED	Evaluating the Safety and Tolerability of Etravirine in HIV-1 Infected Infants and Children
NCT02212379	PHASE2	COMPLETED	Capacity of the Dual Combination Raltegravir/Etravirine to Maintain Virological Success in HIV-1 Infected Patients of at Least 45 Years of Age- ANRS 163 ETRAL
NCT04273165	PHASE2	COMPLETED	Safety and Efficacy of Etravirine in Friedreich Ataxia Patients
NCT00740389	PHASE1	COMPLETED	TMC125-TiDP2-C187: A Phase I, Open-label Trial to Investigate the Pharmacokinetic Interaction Between TMC125 and Two Antifungal Agents (Fluconazole and Voriconazole), All at Steady-state in Healthy Subjects.
NCT00828815	PHASE1	COMPLETED	TMC125-TiDP2-C188: A Phase I, Open-label Trial to Investigate the Pharmacokinetic Effect of Multiple-dose TMC125 on Buprenorphine and Norbuprenorphine Administered in HIV-negative Patients on Stable Buprenorphine/Naloxone Maintenance Therapy.
NCT00855088	PHASE1	COMPLETED	Study in Healthy Males to Measure Darunavir and Etravirine in Blood, Seminal Fluid, and Rectal Tissue
NCT00867152	PHASE1	COMPLETED	GSK1349572 Drug Interaction With Etravirine and Either Darunavir/Ritonavir or Lopinavir/Ritonavir
NCT00871234	PHASE1	COMPLETED	Effects of Etravirine on Endothelial Function in HIV-uninfected Adults: A Pilot Study
NCT01090648	PHASE1	COMPLETED	TMC125HIV1083 - Swallowability of Uncoated 200 mg Etravirine Tablets in HIV-1 Infected Patients
NCT01876966	PHASE1	COMPLETED	Interaction Between Etravirine or Darunavir/Ritonavir and Artemether / Lumefantrine
NCT02063360	PHASE1	COMPLETED	DDI Study of BMS-663068 With Etravirine (ETR) and/or Darunavir (DVR) + Ritonavir (RTV)
NCT02818348	PHASE1	COMPLETED	Clinical Trial to Evaluate Drug-drug Interactions Between Darunavir/Cobicistat and Etravirine in Hiv- Infected Patients

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 1 clinical and 1 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

Related molecules

Related molecules

No competitor molecules sharing a primary target (ChEMBL phase ≥2 or PubChem drug-class).