Efavirenz

Summary

Efavirenz (CHEMBL223228) is an approved small-molecule HIV-1 reverse transcriptase inhibitor (ATC J05AG03) targeting CYP3A4; indicated across 15 conditions including hiv infectious disease and viral infectious disease.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: J05AG03
• Targets: 1 (CYP3A4)
• Indications: 15 conditions
• Clinical trials: 272
• Chemistry: 315.67 Da · C14H9ClF3NO2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL223228
Name	Efavirenz
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	64139
ChEBI	CHEBI:119486
ATC	J05AG03
Molecular formula	C14H9ClF3NO2
Molecular weight	315.67
InChIKey	XPOQHMRABVBWPR-ZDUSSCGKSA-N

SMILES: C1CC1C#C[C@]2(C3=C(C=CC(=C3)Cl)NC(=O)O2)C(F)(F)F

IUPAC name: (4S)-6-chloro-4-(2-cyclopropylethynyl)-4-(trifluoromethyl)-1H-3,1-benzoxazin-2-one

ChEBI definition: 1,4-Dihydro-2H-3,1-benzoxazin-2-one substituted at the 4 position by cyclopropylethynyl and trifluoromethyl groups (S configuration) and at the 6 position by chlorine. A non-nucleoside reverse transcriptase inhibitor with activity against HIV, it is used with other antiretrovirals for combination therapy of HIV infection.

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

Also known as: (-)-efavirenz, DMP-266, Efavirenz, Efavirenz component of atripla, Efavirenz component of symfi, Efavirenz component of telura, Efavirenz teva, Efavirenzum, L-743726, NSC-742403, Stocrin, Sustiva

Patent coverage: 9,332 distinct patent families (35,999 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

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
CYP3A4	CYP3A4	Inhibition	4.76	0%	P08684

Broader ChEMBL bioactivity targets: 25 (assay-derived). Sample: Microtubule-associated protein tau, Nuclear receptor ROR-gamma, Ferritin light chain, Glucocorticoid receptor, Progesterone receptor, Beta-1 adrenergic receptor, Cannabinoid receptor 1, Sodium-dependent noradrenaline transporter, 5-hydroxytryptamine receptor 2A, 5-hydroxytryptamine receptor 2C.

Bioactivity

ChEMBL activities: 8 potent at pChembl ≥ 5 of 28 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
CYP46A1	6.1	Kd	800	nM	CHEMBL_ACT_20644994
NR3C1	5.57	AC50	2710	nM	CHEMBL_ACT_25175990
HTR2A	5.42	AC50	3786	nM	CHEMBL_ACT_25173673
OPRK1	5.31	AC50	4854	nM	CHEMBL_ACT_25129575
CYP46A1	5.3	Kd	5000	nM	CHEMBL_ACT_20645094
HTR2C	5.25	AC50	5612	nM	CHEMBL_ACT_25131964
ADORA3	5.22	AC50	5999	nM	CHEMBL_ACT_25134365
NPSR1	5	Potency	10000	nM	CHEMBL_ACT_4912533

Target pathways

Aggregated over 1 target gene(s): CYP3A4.

Top Reactome pathways

7 total, by targets touching each:

Pathway	Targets	Genes
Phase I - Functionalization of compounds	1	CYP3A4
Xenobiotics	1	CYP3A4
Aflatoxin activation and detoxification	1	CYP3A4
Biosynthesis of maresin-like SPMs	1	CYP3A4
Aspirin ADME	1	CYP3A4
Atorvastatin ADME	1	CYP3A4
Prednisone ADME	1	CYP3A4

Dominant GO biological processes

GO term	Targets
lipid hydroxylation	1
lipid metabolic process	1
steroid catabolic process	1
xenobiotic metabolic process	1
steroid metabolic process	1
cholesterol metabolic process	1
androgen metabolic process	1
estrogen metabolic process	1
alkaloid catabolic process	1
monoterpenoid metabolic process	1
xenobiotic catabolic process	1
vitamin D metabolic process	1
vitamin D catabolic process	1
retinol metabolic process	1
retinoic acid metabolic process	1

Indications & clinical

Indications

15 indications (5 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
autoimmune disease	4	MONDO:0007179	MONDO:0021094
AIDS	3	MONDO:0012268	EFO:0000765
tuberculosis	3	MONDO:0018076	MONDO:0018076
exocrine pancreatic carcinoma	2	MONDO:0005192	EFO:0002618
triple-negative breast carcinoma	2	MONDO:0005494	EFO:0005537
non-Hodgkin lymphoma	1	MONDO:0018908	EFO:0005952
hepatitis C virus infection	1	MONDO:0005231	EFO:0003047
malaria	1	MONDO:0005136	EFO:0001068
type 2 diabetes mellitus	1	MONDO:0005148	MONDO:0005148
neoplasm	1	MONDO:0005070	EFO:0000616

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

Clinical trials

Total trials: 272.

Phase distribution

Phase	Trials
PHASE3	62
PHASE4	51
PHASE2	50
PHASE1	50
Not specified	49
PHASE1/PHASE2	6
PHASE2/PHASE3	3
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00004585	PHASE4	COMPLETED	A Study of the Safety and Effectiveness of Combination Anti-HIV Therapy in HIV-Infected Adults
NCT00005000	PHASE4	UNKNOWN	Treatment With Nelfinavir or Efavirenz of HIV-Infected Patients Who Have Never Received Anti-HIV Drugs
NCT00005017	PHASE4	UNKNOWN	Effectiveness and Safety of Epivir/Ziagen/Zerit (3TC/ABC/d4T) Versus Epivir/Ziagen/Sustiva (3TC/ABC/EFV) Versus Epivir/Ziagen/Agenerase/Norvir (3TC/ABC/APV/RTV) in HIV Patients Who Have Never Received Treatment
NCT00005018	PHASE4	COMPLETED	Safety and Effectiveness of a Combination Anti-HIV Drug Treatment
NCT00006190	PHASE4	COMPLETED	A Study to Determine How and Why HIV-Infected Subjects on Anti-viral Treatment Develop Lipodystrophy
NCT00011895	PHASE4	UNKNOWN	Safety and Effectiveness of TRIZIVIR (Abacavir/Lamivudine/Zidovudine) With Efavirenz in HIV-Infected Patients Who Have Never Taken Anti-HIV Drugs
NCT00084136	PHASE4	COMPLETED	Prospective Evaluation of Anti-retroviral Combinations for Treatment Naive, HIV Infected Persons in Resource-limited Settings
NCT00116116	PHASE4	COMPLETED	DART II - A Phase IV Study of 3 Antiretroviral Medicines in Combination, in HIV Patients Who Have Not Been Previously Treated With Antiretroviral Therapy
NCT00127959	PHASE4	COMPLETED	Virological and Clinical Anti-Hepatitis B Virus (HBV) Efficacy of Tenofovir and Emtricitabine in Patients With HIV/HBV co-Infection
NCT00127972	PHASE4	COMPLETED	2NN & CHARM Long-Term Follow-up Study
NCT00162643	PHASE4	UNKNOWN	PI Vs. NNRTI Based Therapy for HIV Advanced Disease
NCT00192660	PHASE4	COMPLETED	HIV Infection And Metabolic Abnormalities Protocol 1 (HAMA001)
NCT00224458	PHASE4	COMPLETED	Combination of Efavirenz and Truvada - COMET Study
NCT00256828	PHASE4	COMPLETED	Once a Day (QD) - Twice a Day (BID) Clinical Trial: Didanosine, Lamivudine and Efavirenz Versus Zidovudine, Lamivudine and Efavirenz in the Starting Treatment of HIV
NCT00342355	PHASE4	COMPLETED	Antiretroviral Therapy for Advanced HIV Disease in South Africa
NCT00385957	PHASE4	COMPLETED	Immunological and Viral Response to Antiretrovirals in HIV Patients With CD4 Cell Count Below 100
NCT00386659	PHASE4	TERMINATED	Immune Reconstitution in naïve HIV Patients With CD4 <100 Cells/mL When Treated With Lopinavir or Efavirenz.
NCT00442962	PHASE4	COMPLETED	HIV Treatment Reinitiation in Women Who Received Anti-HIV Drugs to Prevent Mother-to-Child Transmission of HIV
NCT00457665	PHASE4	COMPLETED	Mechanisms of Lipodystrophy in HIV-Infected Pateints
NCT00532168	PHASE4	COMPLETED	Once-daily Antiretroviral Therapy in HIV-1 Infected Patients With CD4+ Cell Counts Below 100 Cells/Mcl
NCT00533390	PHASE4	TERMINATED	Randomized Clinical Trial to Assess the Efficacy and Safety of Concomitant Use of Rifampicin and Efavirenz 600 X 800mg
NCT00556634	PHASE4	COMPLETED	Incidence and Severity of Neuropsychiatric Adverse Events of Efavirenz Given as a Stepped Dosage vs. the Usual Dosage
NCT00620438	PHASE4	UNKNOWN	Drug Interaction Between Coartem® and Nevirapine, Efavirenz or Rifampicin in HIV Positive Ugandan Patients
NCT00643968	PHASE4	COMPLETED	Tenofovir DF + Efavirenz (TDF+EFV) Versus Tenofovir DF + Efavirenz + Lamivudine (TDF+EFV+3TC) Maintenance Regimen in Virologically Controlled Patients: COOL Trial
NCT00759070	PHASE4	UNKNOWN	Effects of 2 Initial Standard Antiretroviral Combinations Therapies on Lipid Metabolism
NCT00775606	PHASE4	TERMINATED	Immune Reconstitution of Lopinavir/Ritonavir-Based vs Efavirenz-based HAART in Advanced HIV Disease
NCT00978237	PHASE4	COMPLETED	Clinical Trial to Assess the Effect of the Change of Efavirenz (EFV) for Lopinavir/Ritonavir (LPV/r) in Lipoatrophy in HIV-infected Patients
NCT01014481	PHASE4	TERMINATED	Appropriate Timing of HAART in Co-infected HIV/TB Patients
NCT01075152	PHASE4	COMPLETED	Cryptococcal Optimal ART Timing Trial
NCT01087814	PHASE4	COMPLETED	Sustiva Levels With Use of a Gel Capsule
NCT01147107	PHASE4	COMPLETED	Hepatic Safety of Raltegravir Versus Efavirenz as HIV Therapy for Patients With HIV and HCV Coinfection
NCT01194856	PHASE4	TERMINATED	Switching From Efavirenz to Atazanavir/ Ritonavir in HIV-infected Subjects With Good Virologic Suppression
NCT01270802	PHASE4	COMPLETED	Effects of Switching Efavirenz to Raltegravir on Vascular Function and Bone Markers in HIV-infected Patients
NCT01380080	PHASE4	COMPLETED	REMEMBER: Reducing Early Mortality & Morbidity by Empiric Tuberculosis (TB) Treatment
NCT01445223	PHASE4	COMPLETED	A Study on Antiretroviral Therapy (ART) Naïve Patients On Different Regimens to Treat Hiv (NORTHIV)
NCT01529749	PHASE4	COMPLETED	Effects of Losartan and Antiretroviral Regimen Containing Raltegravir in Fibrosis Inflammation Mediators, Cardiovascular Risk and Neurocognitive Disorders in HIV Infected Patients Previously Effectively Treated
NCT01585038	PHASE4	COMPLETED	Efavirenz Versus Rilpivirine on Vascular Function, Inflammation, and Oxidative Stress
NCT01618305	PHASE4	COMPLETED	Evaluating the Response to Two Antiretroviral Medication Regimens in HIV-Infected Pregnant Women, Who Begin Antiretroviral Therapy Between 20 and 36 Weeks of Pregnancy, for the Prevention of Mother-to-Child Transmission
NCT01704898	PHASE4	COMPLETED	Efavirenz Comparative Bioavailability
NCT01751555	PHASE4	COMPLETED	Efficacy and Safety of TDF+3TC+EFV in Adults With HIV/HBV Coinfection

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

PharmGKB dosing guidelines (2) — CPIC / DPWG genotype-guided dosing for this drug (drug × pharmacogene):

Guideline	Source	Gene(s)	Dosing	Recommendation
Annotation of CPIC Guideline for efavirenz and CYP2B6	CPIC	CYP2B6	yes	yes
Annotation of DPWG Guideline for efavirenz and CYP2B6	DPWG	CYP2B6	yes	yes

PharmGKB also curates 33 clinical and 482 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

584 molecules share ≥1 primary target. Top 60 by shared-target count:

Molecule	Source	Status	Shared targets
DIHYDROERGOTAMINE	ChEMBL + PubChem	Phase 4 (approved)	CYP3A4
Elagolix	ChEMBL + PubChem	Phase 4 (approved)	CYP3A4
SAXAGLIPTIN	ChEMBL + PubChem	Phase 4 (approved)	CYP3A4
ABIRATERONE	ChEMBL	Phase 4 (approved)	CYP3A4
ACETAMINOPHEN	ChEMBL	Phase 4 (approved)	CYP3A4
ACRISORCIN	ChEMBL	Phase 4 (approved)	CYP3A4
ALOSETRON	ChEMBL	Phase 4 (approved)	CYP3A4
AMINOGLUTETHIMIDE	ChEMBL	Phase 4 (approved)	CYP3A4
AMIODARONE	ChEMBL	Phase 4 (approved)	CYP3A4
AMITRIPTYLINE	ChEMBL	Phase 4 (approved)	CYP3A4
AMLODIPINE	ChEMBL	Phase 4 (approved)	CYP3A4
AMOXAPINE	ChEMBL	Phase 4 (approved)	CYP3A4
AMPICILLIN	ChEMBL	Phase 4 (approved)	CYP3A4
AMPRENAVIR	ChEMBL	Phase 4 (approved)	CYP3A4
AMSACRINE	ChEMBL	Phase 4 (approved)	CYP3A4
APOMORPHINE	ChEMBL	Phase 4 (approved)	CYP3A4
APREPITANT	ChEMBL	Phase 4 (approved)	CYP3A4
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	CYP3A4
ATOMOXETINE	ChEMBL	Phase 4 (approved)	CYP3A4
ATORVASTATIN	ChEMBL	Phase 4 (approved)	CYP3A4
AZATHIOPRINE	ChEMBL	Phase 4 (approved)	CYP3A4
AZELASTINE	ChEMBL	Phase 4 (approved)	CYP3A4
AZITHROMYCIN	ChEMBL	Phase 4 (approved)	CYP3A4
BACLOFEN	ChEMBL	Phase 4 (approved)	CYP3A4
BENDROFLUMETHIAZIDE	ChEMBL	Phase 4 (approved)	CYP3A4
BENZBROMARONE	ChEMBL	Phase 4 (approved)	CYP3A4
BENZNIDAZOLE	ChEMBL	Phase 4 (approved)	CYP3A4
BENZONATATE	ChEMBL	Phase 4 (approved)	CYP3A4
BENZTHIAZIDE	ChEMBL	Phase 4 (approved)	CYP3A4
BEPRIDIL	ChEMBL	Phase 4 (approved)	CYP3A4
BERBERINE	ChEMBL	Phase 4 (approved)	CYP3A4
BIFONAZOLE	ChEMBL	Phase 4 (approved)	CYP3A4
BITHIONOL	ChEMBL	Phase 4 (approved)	CYP3A4
BITHIONOLATE	ChEMBL	Phase 4 (approved)	CYP3A4
BRETYLIUM TOSYLATE	ChEMBL	Phase 4 (approved)	CYP3A4
BROMHEXINE	ChEMBL	Phase 4 (approved)	CYP3A4
BROMOCRIPTINE	ChEMBL	Phase 4 (approved)	CYP3A4
BROMPERIDOL	ChEMBL	Phase 4 (approved)	CYP3A4
BUDESONIDE	ChEMBL	Phase 4 (approved)	CYP3A4
BUPIVACAINE	ChEMBL	Phase 4 (approved)	CYP3A4
BUSPIRONE	ChEMBL	Phase 4 (approved)	CYP3A4
BUTAMBEN	ChEMBL	Phase 4 (approved)	CYP3A4
CANDESARTAN CILEXETIL	ChEMBL	Phase 4 (approved)	CYP3A4
CANNABIDIOL	ChEMBL	Phase 4 (approved)	CYP3A4
CAPSAICIN	ChEMBL	Phase 4 (approved)	CYP3A4
CARBETAPENTANE	ChEMBL	Phase 4 (approved)	CYP3A4
CARBIDOPA	ChEMBL	Phase 4 (approved)	CYP3A4
CARFILZOMIB	ChEMBL	Phase 4 (approved)	CYP3A4
CARISOPRODOL	ChEMBL	Phase 4 (approved)	CYP3A4
CEFDITOREN PIVOXIL	ChEMBL	Phase 4 (approved)	CYP3A4
CELECOXIB	ChEMBL	Phase 4 (approved)	CYP3A4
CHLORAMPHENICOL	ChEMBL	Phase 4 (approved)	CYP3A4
CHLOROXINE	ChEMBL	Phase 4 (approved)	CYP3A4
CHLORPROMAZINE	ChEMBL	Phase 4 (approved)	CYP3A4
CHLORPROPAMIDE	ChEMBL	Phase 4 (approved)	CYP3A4
CHOLECALCIFEROL	ChEMBL	Phase 4 (approved)	CYP3A4
CHOLIC ACID	ChEMBL	Phase 4 (approved)	CYP3A4
CIMETIDINE	ChEMBL	Phase 4 (approved)	CYP3A4
CINNARIZINE	ChEMBL	Phase 4 (approved)	CYP3A4
CISAPRIDE	ChEMBL	Phase 4 (approved)	CYP3A4