Tox | Related Drugs | BioActivity |

Stem definition	Drug id	CAS RN
antivirals Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI)	1115	269055-15-4

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: etravirine intelence etravirin R-165335 TMC-125	HIV-1 reverse transriptase inhibitor; an anti-HIV agent Molecular weight: 435.29 Formula: C20H15BrN6O CLOGP: 5.17 LIPINSKI: 1 HAC: 7 HDO: 2 TPSA: 120.64 ALOGS: -4.41 ROTB: 4 Status: OFP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

etravirine
intelence
etravirin
R-165335
TMC-125

HIV-1 reverse transriptase inhibitor; an anti-HIV agent

Molecular weight: 435.29
Formula: C20H15BrN6O
CLOGP: 5.17
LIPINSKI: 1
HAC: 7
HDO: 2
TPSA: 120.64
ALOGS: -4.41
ROTB: 4

Status: OFP

Legend:
OFP - off patent
OFM - off market
ONP - on patent

Drug dosage:

Dose	Unit	Route
0.40	g	O

ADMET properties:

Property	Value	Reference
BDDCS (Biopharmaceutical Drug Disposition Classification System)	2	Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine)	0 %	Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose)	6.56 µM/kg/day	Contrera JF, Matthews EJ, Kruhlak NL, Benz RD

Predicted pharmacokinetic/toxicological properties (PK-AZ):

Property	Description	Value	Unit	Confidence	Similarity
azlogd74	LogD at pH 7.4	4.727		High	1
caco2-efflux	Caco-2 efflux ratio (BA/AB)	1.247		High	1
caco2-intrinsic-papp	Caco-2 intrinsic apparent permeability	12.853	10^-6 cm/s	High	1
dh-clint	Dog hepatocyte intrinsic clearance	14.355	uL/min/10^6 cells	High	1
dppb	Dog plasma protein binding (% unbound)	0.290	%	High	1
fcs-ppb	Fetal calf serum protein binding (% unbound)	0.820	%	High	1
herg	hERG pIC50	5.541	pIC50	High	1
hh-clint	Human hepatocyte intrinsic clearance	7.295	uL/min/10^6 cells	High	1
hlm-clint	Human liver microsomal intrinsic clearance	7.907	uL/min/mg protein	High	1
hppb	Human plasma protein binding (% unbound)	0.310	%	High	1
mdck-mdr1-efflux	MDCK-MDR1 efflux ratio	1.531		High	1
mh-clint	Mouse hepatocyte intrinsic clearance	37.068		High	1
mppb	Mouse plasma protein binding (% unbound)	0.290		High	1
nih-mdck-mdr1-efflux	NIH MDCK-MDR1 efflux ratio	1.687		High	1
pfas-class	PFAS structural alert (1 = True, 0 = False)	0
pppb	Pig plasma protein binding (% unbound)	0.520	%	High	1
rh-clint	Rat hepatocyte intrinsic clearance	17.179	uL/min/10^6 cells	High	1
rh-fuinc	Rat hepatocyte fraction unbound in incubation	1.650	%	High	1
rppb	Rat plasma protein binding (% unbound)	0.250	%	High	1
solubility-dd	Solubility at pH 7.4 in DMSO	0.649	uM	High	1

Approvals:

Date	Agency	Company	Orphan
Aug. 28, 2008	EMA
Jan. 18, 2008	FDA	JANSSEN R AND D

FDA Adverse Event Reporting System (Female)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Enlarged clitoris	217.82	40.58	28	2573	123	90625723
Viral mutation identified	215.20	40.58	39	2562	1986	90623860
Virologic failure	198.74	40.58	37	2564	2187	90623659
Hyperandrogenism	197.17	40.58	25	2576	96	90625750
Foetal exposure during pregnancy	171.08	40.58	59	2542	42916	90582930
Exposure during pregnancy	163.28	40.58	95	2506	238315	90387531
Lipodystrophy acquired	140.42	40.58	26	2575	1488	90624358
Cloacal exstrophy	122.12	40.58	17	2584	149	90625697
Congenital genital malformation	121.42	40.58	17	2584	156	90625690
Abortion spontaneous	115.27	40.58	47	2554	54009	90571837
Bladder agenesis	114.65	40.58	16	2585	143	90625703
Genitalia external ambiguous	113.96	40.58	16	2585	150	90625696
Caudal regression syndrome	111.06	40.58	16	2585	183	90625663
Gastrointestinal disorder congenital	107.39	40.58	15	2586	135	90625711
Anal atresia	105.17	40.58	17	2584	433	90625413
Tethered cord syndrome	104.82	40.58	16	2585	278	90625568
Gastrointestinal malformation	102.20	40.58	15	2586	197	90625649
Meconium stain	102.06	40.58	15	2586	199	90625647
Meningomyelocele	99.14	40.58	17	2584	625	90625221
Exomphalos	94.26	40.58	16	2585	553	90625293
Umbilical cord abnormality	91.37	40.58	16	2585	666	90625180
Premature baby	86.55	40.58	31	2570	25046	90600800
Premature labour	84.11	40.58	26	2575	13350	90612496
Pathogen resistance	82.96	40.58	23	2578	8092	90617754
Drug resistance	73.59	40.58	29	2572	30420	90595426
Immune reconstitution inflammatory syndrome	72.24	40.58	20	2581	6999	90618847
Neural tube defect	71.74	40.58	11	2590	197	90625649
Spina bifida	55.89	40.58	11	2590	869	90624977
Treatment noncompliance	55.86	40.58	28	2573	51699	90574147
Congenital ectopic bladder	54.50	40.58	8	2593	105	90625741
Anencephaly	51.05	40.58	9	2592	389	90625457
Sepsis neonatal	47.17	40.58	9	2592	604	90625242
Amniotic cavity infection	45.26	40.58	10	2591	1386	90624460
Adrenogenital syndrome	43.58	40.58	6	2595	48	90625798
Congenital anomaly	42.70	40.58	13	2588	6334	90619512

FDA Adverse Event Reporting System (Male)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Lipodystrophy acquired	455.78	23.37	101	5005	3349	42612880
Mitochondrial toxicity	414.88	23.37	89	5017	2526	42613703
Progressive external ophthalmoplegia	401.24	23.37	78	5028	1333	42614896
Eyelid ptosis	336.88	23.37	90	5016	6571	42609658
Virologic failure	245.32	23.37	63	5043	3931	42612298
Diplopia	220.13	23.37	85	5021	20231	42595998
Drug interaction	163.39	23.37	179	4927	266820	42349409
Viral mutation identified	144.86	23.37	40	5066	3291	42612938
Drug resistance	105.37	23.37	60	5046	34188	42582041
Ophthalmoplegia	102.98	23.37	28	5078	2172	42614057
Pathogen resistance	73.43	23.37	33	5073	11417	42604812
Adrenal suppression	67.99	23.37	17	5089	948	42615281
CD4 lymphocytes decreased	65.12	23.37	19	5087	1902	42614327
Immune reconstitution inflammatory syndrome	45.90	23.37	23	5083	10120	42606109
Drug level increased	45.52	23.37	32	5074	26168	42590061
Cytomegalovirus chorioretinitis	45.29	23.37	18	5088	4593	42611636
Fibrous histiocytoma	44.63	23.37	10	5096	346	42615883
Multiple-drug resistance	43.45	23.37	20	5086	7302	42608927
Viral load increased	41.37	23.37	15	5091	2982	42613247
Osteoporosis	35.07	23.37	22	5084	14884	42601345
Heart transplant rejection	34.21	23.37	11	5095	1523	42614706
Renal tubular disorder	34.19	23.37	15	5091	4894	42611335
Blood creatine phosphokinase abnormal	33.20	23.37	8	5098	382	42615847
Dyslipidaemia	33.01	23.37	18	5088	9400	42606829
Hepatic steatosis	32.24	23.37	24	5082	21424	42594805
Drug level decreased	32.04	23.37	18	5088	9959	42606270
Hepatic cirrhosis	31.77	23.37	23	5083	19679	42596550
Hepatitis	29.17	23.37	25	5081	27275	42588954
Hepatitis C	29.11	23.37	17	5089	10116	42606113
Choroiditis	27.18	23.37	9	5097	1366	42614863
Mycobacterium avium complex infection	26.91	23.37	11	5095	3016	42613213
Lipohypertrophy	24.69	23.37	6	5100	297	42615932
Genotype drug resistance test positive	24.28	23.37	8	5098	1196	42615033
Anogenital dysplasia	23.44	23.37	5	5101	137	42616092

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Lipodystrophy acquired	547.94	25.03	107	5704	4417	110579071
Progressive external ophthalmoplegia	471.84	25.03	79	5732	1341	110582147
Mitochondrial toxicity	462.51	25.03	88	5723	3157	110580331
Virologic failure	356.21	25.03	76	5735	4876	110578612
Eyelid ptosis	333.88	25.03	87	5724	13240	110570248
Viral mutation identified	324.55	25.03	69	5742	4350	110579138
Diplopia	228.35	25.03	85	5726	41809	110541679
Drug interaction	206.48	25.03	186	5625	499997	110083491
Drug resistance	154.73	25.03	70	5741	56304	110527184
Pathogen resistance	126.85	25.03	44	5767	17628	110565860
Ophthalmoplegia	107.57	25.03	27	5784	3523	110579965
Immune reconstitution inflammatory syndrome	95.97	25.03	35	5776	16191	110567297
Multiple-drug resistance	79.95	25.03	29	5782	13206	110570282
Adrenal suppression	77.66	25.03	18	5793	1678	110581810
Abortion spontaneous	64.85	25.03	33	5778	34249	110549239
Treatment noncompliance	57.73	25.03	40	5771	72950	110510538
Blood HIV RNA increased	53.36	25.03	14	5797	2174	110581314
Exposure during pregnancy	49.35	25.03	52	5759	167372	110416116
CD4 lymphocytes decreased	44.65	25.03	13	5798	2961	110580527
Fibrous histiocytoma	44.30	25.03	10	5801	829	110582659
Renal tubular disorder	43.82	25.03	16	5795	7413	110576075
Hepatitis C	42.18	25.03	18	5793	12555	110570933
Dyslipidaemia	41.15	25.03	19	5792	15946	110567542
Mycobacterium avium complex infection	39.72	25.03	14	5797	5863	110577625
Genotype drug resistance test positive	39.16	25.03	10	5801	1396	110582092
Drug level decreased	35.49	25.03	18	5793	18530	110564958
Hepatic cirrhosis	33.41	25.03	28	5783	67598	110515890
Choroiditis	33.07	25.03	9	5802	1606	110581882
Premature labour	30.33	25.03	13	5798	9159	110574329
Hepatic steatosis	30.05	25.03	23	5788	48808	110534680
Superinfection bacterial	29.54	25.03	9	5802	2392	110581096
Amniotic cavity infection	27.98	25.03	7	5804	900	110582588
Oesophageal candidiasis	27.47	25.03	13	5798	11521	110571967
Lipohypertrophy	27.26	25.03	7	5804	999	110582489
Anogenital dysplasia	26.48	25.03	5	5806	171	110583317
Drug level increased	26.17	25.03	21	5790	47698	110535790

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

Source	Code	Description
ATC	J05AG04	ANTIINFECTIVES FOR SYSTEMIC USE ANTIVIRALS FOR SYSTEMIC USE DIRECT ACTING ANTIVIRALS Non-nucleoside reverse transcriptase inhibitors
FDA MoA	N0000009948	Non-Nucleoside Reverse Transcriptase Inhibitors
FDA EXT	N0000175460	Non-Nucleoside Analog
FDA EPC	N0000175463	Human Immunodeficiency Virus 1 Non-Nucleoside Analog Reverse Transcriptase Inhibitor
MeSH PA	D000890	Anti-Infective Agents
MeSH PA	D000998	Antiviral Agents
MeSH PA	D004791	Enzyme Inhibitors
MeSH PA	D018894	Reverse Transcriptase Inhibitors
MeSH PA	D019384	Nucleic Acid Synthesis Inhibitors
FDA MoA	N0000182140	Cytochrome P450 2C19 Inhibitors
FDA MoA	N0000185503	P-Glycoprotein Inhibitors
FDA MoA	N0000185504	Cytochrome P450 2C9 Inhibitors
FDA MoA	N0000190118	Cytochrome P450 3A Inducers
CHEBI has role	CHEBI:22587	antiviral agent
CHEBI has role	CHEBI:35441	antiinfective agent
CHEBI has role	CHEBI:53756	HIV-1 reverse transcriptase inhibitor
CHEBI has role	CHEBI:64946	anti-HIV agent

Related Drugs by ATC class:

J05AG Non-nucleoside reverse transcriptase inhibitors 5 drugs

delavirdine doravirine efavirenz nevirapine rilpivirine

Drug Use | Suggest Off label Use Form| |View source of the data|

Disease	Relation	SNOMED_ID	DOID
Human immunodeficiency virus infection	indication	86406008	DOID:526
Chronic type B viral hepatitis	contraindication	61977001
Chronic hepatitis C	contraindication	128302006
Liver function tests abnormal	contraindication	166603001
Peripheral nerve disease	contraindication	302226006
Breastfeeding (mother)	contraindication	413712001

🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	3.78	Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Bioact source	MoA source
Multidrug resistance protein 1	Transporter	P08183	MDR1_HUMAN		IC50	5.12	CHEMBL
Canalicular multispecific organic anion transporter 1	Transporter	Q92887	MRP2_HUMAN		IC50	5.11	CHEMBL
Multidrug resistance-associated protein 1	Transporter	P33527	MRP1_HUMAN		IC50	5.07	CHEMBL
ATP-binding cassette sub-family G member 2	Transporter	Q9UNQ0	ABCG2_HUMAN		IC50	5.22	CHEMBL
Canalicular multispecific organic anion transporter 2	Transporter	O15438	MRP3_HUMAN		IC50	5.29	CHEMBL
Reverse transcriptase/RNaseH	Enzyme		Q72547_9HIV1	INHIBITOR	IC50	9.22	CHEMBL	CHEMBL
Gag-Pol polyprotein	Polyprotein		POL_HV1A2		IC50	9	WOMBAT-PK
Cruzipain	Enzyme		CYSP_TRYCR		IC50	5.40	CHEMBL
Reverse transcriptase	Enzyme		Q9WKE8_9HIV1		IC50	8	CHEMBL
Reverse transcriptase protein	Enzyme		Q9WJQ2_9HIV1		IC50	8.89	CHEMBL

External reference:

ID	Source
4027244	VUID
N0000179781	NUI
D04112	KEGG_DRUG
4027244	VANDF
C1456409	UMLSCUI
CHEBI:63589	CHEBI
65B	PDB_CHEM_ID
CHEMBL308954	ChEMBL_ID
DB06414	DRUGBANK_ID
C451734	MESH_SUPPLEMENTAL_RECORD_UI
12675	IUPHAR_LIGAND_ID
8303	INN_ID
0C50HW4FO1	UNII
193962	PUBCHEM_CID
475969	RXNORM
130981	MMSL
24971	MMSL
348481	MMSL
d07076	MMSL
012527	NDDF
432121008	SNOMEDCT_US
432221004	SNOMEDCT_US
0C50HW4FO1	INXIGHT DRUGS

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
Etravirine	HUMAN PRESCRIPTION DRUG LABEL	1	10147-0570	TABLET	100 mg	ORAL	NDA	32 sections
Etravirine	HUMAN PRESCRIPTION DRUG LABEL	1	10147-0571	TABLET	200 mg	ORAL	NDA	32 sections
etravirine	HUMAN PRESCRIPTION DRUG LABEL	1	42291-473	TABLET	100 mg	ORAL	ANDA	25 sections
etravirine	HUMAN PRESCRIPTION DRUG LABEL	1	42291-474	TABLET	200 mg	ORAL	ANDA	25 sections
Intelence	HUMAN PRESCRIPTION DRUG LABEL	1	53808-0787	TABLET	100 mg	ORAL	NDA	31 sections
Intelence	HUMAN PRESCRIPTION DRUG LABEL	1	54868-5864	TABLET	100 mg	ORAL	NDA	30 sections
Intelence	HUMAN PRESCRIPTION DRUG LABEL	1	54868-6368	TABLET	200 mg	ORAL	NDA	30 sections
Intelence	HUMAN PRESCRIPTION DRUG LABEL	1	59676-570	TABLET	100 mg	ORAL	NDA	30 sections
Intelence	HUMAN PRESCRIPTION DRUG LABEL	1	59676-571	TABLET	200 mg	ORAL	NDA	30 sections
Intelence	HUMAN PRESCRIPTION DRUG LABEL	1	59676-572	TABLET	25 mg	ORAL	NDA	30 sections
etravirine	HUMAN PRESCRIPTION DRUG LABEL	1	60219-1720	TABLET	25 mg	ORAL	ANDA	26 sections
etravirine	HUMAN PRESCRIPTION DRUG LABEL	1	60219-1721	TABLET	100 mg	ORAL	ANDA	26 sections
etravirine	HUMAN PRESCRIPTION DRUG LABEL	1	60219-1722	TABLET	200 mg	ORAL	ANDA	26 sections
etravirine	HUMAN PRESCRIPTION DRUG LABEL	1	69238-1720	TABLET	25 mg	ORAL	ANDA	26 sections
etravirine	HUMAN PRESCRIPTION DRUG LABEL	1	69238-1721	TABLET	100 mg	ORAL	ANDA	26 sections
etravirine	HUMAN PRESCRIPTION DRUG LABEL	1	69238-1722	TABLET	200 mg	ORAL	ANDA	26 sections
ETRAVIRINE	HUMAN PRESCRIPTION DRUG LABEL	1	69315-285	TABLET	100 mg	ORAL	ANDA	22 sections
ETRAVIRINE	HUMAN PRESCRIPTION DRUG LABEL	1	69315-286	TABLET	200 mg	ORAL	ANDA	22 sections
etravirine	HUMAN PRESCRIPTION DRUG LABEL	1	69452-254	TABLET	100 mg	ORAL	ANDA	29 sections
etravirine	HUMAN PRESCRIPTION DRUG LABEL	1	69452-255	TABLET	200 mg	ORAL	ANDA	29 sections
ETRAVIRINE	HUMAN PRESCRIPTION DRUG LABEL	1	80005-112	TABLET	100 mg	ORAL	ANDA	22 sections
ETRAVIRINE	HUMAN PRESCRIPTION DRUG LABEL	1	80005-113	TABLET	200 mg	ORAL	ANDA	22 sections