U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C22H18N6
Molecular Weight 366.4185
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of RILPIVIRINE

SMILES

CC1=CC(\C=C\C#N)=CC(C)=C1NC2=NC(NC3=CC=C(C=C3)C#N)=NC=C2

InChI

InChIKey=YIBOMRUWOWDFLG-ONEGZZNKSA-N
InChI=1S/C22H18N6/c1-15-12-18(4-3-10-23)13-16(2)21(15)27-20-9-11-25-22(28-20)26-19-7-5-17(14-24)6-8-19/h3-9,11-13H,1-2H3,(H2,25,26,27,28)/b4-3+

HIDE SMILES / InChI

Description
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/?term=19933797

Rilpivirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) which is used for the treatment of HIV-1 infections in treatment-naive patients. It is active against wild-type and NNRTI-resistant HIV-1. Rilpivirine is a diarylpyrimidinethat inhibits HIV-1 replication by non-competitive inhibition of HIV-1 reverse transcriptase (RT). Rilpivirine does not inhibit the human cellular DNA polymerases α, β and γ.

CNS Activity

CNS Active
3913
Curator's Comment: Common side effects may include Central Nervous System (CNS) related side effects including dizziness, difficulty with concentration, sleep disturbances, vivid dreams, agitation, nausea (upset stomach, feeling sick to the stomach), dizziness, sleep disturbances.

Originator

Approval Year

2011
587
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8297
 14.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Approved
8429
EDURANT

Approved Use

In combination with other antiretroviral agents, is indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in antiretroviral treatment-naïve patients with HIV-1 RNA less than or equal to 100,000 copies/mL at the start of therapy.

Launch Date

1.30584963E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
0.14 μg/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/27187753/
25 mg 1 times / day multiple, oral
dose: 25 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
RILPIVIRINE plasma
Homo sapiens
population: UNHEALTHY
age: ADOLESCENT
sex: FEMALE / MALE
food status: FED
121 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/29335895/
25 mg 1 times / day multiple, oral
dose: 25 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
RILPIVIRINE plasma
Homo sapiens
population: PREGNANT
age: ADULT
sex: FEMALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
2.38 μg × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/27187753/
25 mg 1 times / day multiple, oral
dose: 25 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
RILPIVIRINE plasma
Homo sapiens
population: UNHEALTHY
age: ADOLESCENT
sex: FEMALE / MALE
food status: FED
1792 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/29335895/
25 mg 1 times / day multiple, oral
dose: 25 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
RILPIVIRINE plasma
Homo sapiens
population: PREGNANT
age: ADULT
sex: FEMALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
0.3%
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/29335895/
25 mg 1 times / day multiple, oral
dose: 25 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
RILPIVIRINE plasma
Homo sapiens
population: PREGNANT
age: ADULT
sex: FEMALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
150 mg 1 times / day multiple, oral
Highest studied dose
Dose: 150 mg, 1 times / day
Route: oral
Route: multiple
Dose: 150 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/19926964
Page: p.62
unhealthy, 21–66
n = 91
Health Status: unhealthy
Condition: HIV-1 infection
Age Group: 21–66
Sex: M+F
Population Size: 91
Sources:
https://pubmed.ncbi.nlm.nih.gov/19926964
Page: p.62
Disc. AE: Alanine aminotransferase increase, Aspartate aminotransferase increased...
AEs leading to
discontinuation/dose reduction:
Alanine aminotransferase increase
Aspartate aminotransferase increased
Sources:
https://pubmed.ncbi.nlm.nih.gov/19926964
Page: p.62
25 mg 1 times / day multiple, oral
Recommended
Dose: 25 mg, 1 times / day
Route: oral
Route: multiple
Dose: 25 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202022s000lbl.pdf
Page: p.1
unhealthy
n = 686
Health Status: unhealthy
Condition: HIV-1 infection
Population Size: 686
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202022s000lbl.pdf
Page: p.1
Disc. AE: Depressive disorders, Suicide attempt...
AEs leading to
discontinuation/dose reduction:
Depressive disorders (severe, 1%)
Suicide attempt (0.29%)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202022s000lbl.pdf
Page: p.1
25 mg 1 times / day multiple, oral
Recommended
Dose: 25 mg, 1 times / day
Route: oral
Route: multiple
Dose: 25 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202022s000lbl.pdf
Page: p.3
unhealthy
n = 686
Health Status: unhealthy
Condition: HIV-1 infection
Population Size: 686
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202022s000lbl.pdf
Page: p.3
Disc. AE: Rash...
AEs leading to
discontinuation/dose reduction:
Rash (0.1%)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202022s000lbl.pdf
Page: p.3
25 mg 1 times / day multiple, oral
Recommended
Dose: 25 mg, 1 times / day
Route: oral
Route: multiple
Dose: 25 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202022s000lbl.pdf
Page: p.1
unhealthy
Health Status: unhealthy
Condition: HIV-1 infection
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202022s000lbl.pdf
Page: p.1
Disc. AE: Fat redistribution, Immune reconstitution syndrome...
AEs leading to
discontinuation/dose reduction:
Fat redistribution
Immune reconstitution syndrome
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202022s000lbl.pdf
Page: p.1
AEs

AEs

AESignificanceDosePopulation
Alanine aminotransferase increase Disc. AE
150 mg 1 times / day multiple, oral
Highest studied dose
Dose: 150 mg, 1 times / day
Route: oral
Route: multiple
Dose: 150 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/19926964
Page: p.62
unhealthy, 21–66
n = 91
Health Status: unhealthy
Condition: HIV-1 infection
Age Group: 21–66
Sex: M+F
Population Size: 91
Sources:
https://pubmed.ncbi.nlm.nih.gov/19926964
Page: p.62
Aspartate aminotransferase increased Disc. AE
150 mg 1 times / day multiple, oral
Highest studied dose
Dose: 150 mg, 1 times / day
Route: oral
Route: multiple
Dose: 150 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/19926964
Page: p.62
unhealthy, 21–66
n = 91
Health Status: unhealthy
Condition: HIV-1 infection
Age Group: 21–66
Sex: M+F
Population Size: 91
Sources:
https://pubmed.ncbi.nlm.nih.gov/19926964
Page: p.62
Suicide attempt 0.29%
Disc. AE
25 mg 1 times / day multiple, oral
Recommended
Dose: 25 mg, 1 times / day
Route: oral
Route: multiple
Dose: 25 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202022s000lbl.pdf
Page: p.1
unhealthy
n = 686
Health Status: unhealthy
Condition: HIV-1 infection
Population Size: 686
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202022s000lbl.pdf
Page: p.1
Depressive disorders severe, 1%
Disc. AE
25 mg 1 times / day multiple, oral
Recommended
Dose: 25 mg, 1 times / day
Route: oral
Route: multiple
Dose: 25 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202022s000lbl.pdf
Page: p.1
unhealthy
n = 686
Health Status: unhealthy
Condition: HIV-1 infection
Population Size: 686
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202022s000lbl.pdf
Page: p.1
Rash 0.1%
Disc. AE
25 mg 1 times / day multiple, oral
Recommended
Dose: 25 mg, 1 times / day
Route: oral
Route: multiple
Dose: 25 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202022s000lbl.pdf
Page: p.3
unhealthy
n = 686
Health Status: unhealthy
Condition: HIV-1 infection
Population Size: 686
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202022s000lbl.pdf
Page: p.3
Fat redistribution Disc. AE
25 mg 1 times / day multiple, oral
Recommended
Dose: 25 mg, 1 times / day
Route: oral
Route: multiple
Dose: 25 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202022s000lbl.pdf
Page: p.1
unhealthy
Health Status: unhealthy
Condition: HIV-1 infection
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202022s000lbl.pdf
Page: p.1
Immune reconstitution syndrome Disc. AE
25 mg 1 times / day multiple, oral
Recommended
Dose: 25 mg, 1 times / day
Route: oral
Route: multiple
Dose: 25 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202022s000lbl.pdf
Page: p.1
unhealthy
Health Status: unhealthy
Condition: HIV-1 infection
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202022s000lbl.pdf
Page: p.1
Sourcing

Sourcing

Vendor/AggregatorIDURL
ChEBI
CHEBI:68606
https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:68606
ChemicalBook
CB81454833
https://www.chemicalbook.com/ChemicalProductProperty_EN_CB81454833
MolPort
MolPort-006-170-051
https://www.molport.com/shop/molecule-link/MolPort-006-170-051
ZINC
ZINC000001554274
http://zinc15.docking.org/substances/ZINC000001554274
eMolecules
10663308
https://www.emolecules.com/cgi-bin/more?vid=10663308
PubMed

PubMed

TitleDatePubMed
A series of diaryltriazines and diarylpyrimidines are highly potent nonnucleoside reverse transcriptase inhibitors with possible applications as microbicides.
2004 Oct
Synthesis of novel diarylpyrimidine analogues and their antiviral activity against human immunodeficiency virus type 1.
2005 Mar 24
In search of a novel anti-HIV drug: multidisciplinary coordination in the discovery of 4-[[4-[[4-[(1E)-2-cyanoethenyl]-2,6-dimethylphenyl]amino]-2- pyrimidinyl]amino]benzonitrile (R278474, rilpivirine).
2005 Mar 24
Next-generation HIV-1 non-nucleoside reverse transcriptase inhibitors.
2006 Feb
Synthesis of novel diarylpyrimidine analogues of TMC278 and their antiviral activity against HIV-1 wild-type and mutant strains.
2007 May
Rilpivirine: a novel non-nucleoside reverse transcriptase inhibitor.
2009 Jul
TMC278, a next-generation nonnucleoside reverse transcriptase inhibitor (NNRTI), active against wild-type and NNRTI-resistant HIV-1.
2010 Feb
Design, synthesis, and preclinical evaluations of novel 4-substituted 1,5-diarylanilines as potent HIV-1 non-nucleoside reverse transcriptase inhibitor (NNRTI) drug candidates.
2012 Aug 23
Rational design of potent non-nucleoside inhibitors of HIV-1 reverse transcriptase.
2012 Dec 13
Rilpivirine: a next-generation non-nucleoside analogue for the treatment of HIV infection.
2012 May
Potential of the novel antiretroviral drug rilpivirine to modulate the expression and function of drug transporters and drug-metabolising enzymes in vitro.
2013 May
Update on rilpivirine: a new potent non-nucleoside reverse transcriptase inhibitor (NNRTI) of HIV replication.
2013 May
In vitro and in vivo activities of AIC292, a novel HIV-1 nonnucleoside reverse transcriptase inhibitor.
2013 Nov
Optimization of diarylazines as anti-HIV agents with dramatically enhanced solubility.
2013 Sep 15
Competitive fitness assays indicate that the E138A substitution in HIV-1 reverse transcriptase decreases in vitro susceptibility to emtricitabine.
2014
In vitro characterization of MK-1439, a novel HIV-1 nonnucleoside reverse transcriptase inhibitor.
2014
Discovery of MK-1439, an orally bioavailable non-nucleoside reverse transcriptase inhibitor potent against a wide range of resistant mutant HIV viruses.
2014 Feb 1
Patents

Patents

20040198739
2
JP2007520443A
12
JP4822707B2
2

Sample Use Guides

In Vivo Use Guide
25 mg (one 25 mg tablet) taken once daily with a meal, is not recommended for patients less than 12 years of age. With rifabutin co-administration, the Edurant dose should be increased to 50 mg (two tablets of 25 mg each) taken once daily with a meal.
Route of Administration: Oral
In Vitro Use Guide
TMC278 (rilpivirine) showed subnanomolar 50% effective concentrations (EC50 values) against wild-type HIV-1 group M isolates (0.07 to 1.01 nM) and nanomolar EC50 values against group O isolates (2.88 to 8.45 nM).
Name Type Language
RILPIVIRINE
DASH   INN   MART.   MI   ORANGE BOOK   USAN   VANDF   WHO-DD  
INN   USAN  
Official Name English
Rilpivirine [WHO-DD]
Common Name English
R278474
Code English
RILPIVIRINE COMPONENT OF CABENUVA
Brand Name English
rilpivirine [INN]
Common Name English
R-278474
Code English
TMC-278
Code English
4-{[4-({4-[(1E)-2-Cyanoethenyl]-2,6-dimethylphenyl}amino)pyrimidin-2-yl]amino}benzonitrile
Systematic Name English
RILPIVIRINE [USAN]
Common Name English
RILPIVIRINE [MI]
Common Name English
EDURANT
Brand Name English
BENZONITRILE, 4-((4-((4-((1E)-2-CYANOETHENYL)-2,6-DIMETHYLPHENYL)AMINO)-2- PYRIMIDINYL)AMINO)-
Systematic Name English
CABENUVA COMPONENT RILPIVIRINE
Brand Name English
RILPIVIRINE [VANDF]
Common Name English
RILPIVIRINE [MART.]
Common Name English
RILPIVIRINE [JAN]
Common Name English
TMC278
Code English
RILPIVIRINE [ORANGE BOOK]
Common Name English
Classification Tree Code System Code
WHO-ATC J05AG05
Created by admin on Fri Dec 15 16:22:05 UTC 2023 , Edited by admin on Fri Dec 15 16:22:05 UTC 2023
WHO-ATC J05AR08
Created by admin on Fri Dec 15 16:22:05 UTC 2023 , Edited by admin on Fri Dec 15 16:22:05 UTC 2023
FDA ORPHAN DRUG 858321
Created by admin on Fri Dec 15 16:22:05 UTC 2023 , Edited by admin on Fri Dec 15 16:22:05 UTC 2023
NDF-RT N0000175463
Created by admin on Fri Dec 15 16:22:05 UTC 2023 , Edited by admin on Fri Dec 15 16:22:05 UTC 2023
NCI_THESAURUS C97453
Created by admin on Fri Dec 15 16:22:05 UTC 2023 , Edited by admin on Fri Dec 15 16:22:05 UTC 2023
WHO-VATC QJ05AG05
Created by admin on Fri Dec 15 16:22:05 UTC 2023 , Edited by admin on Fri Dec 15 16:22:05 UTC 2023
WHO-ATC J05AR19
Created by admin on Fri Dec 15 16:22:05 UTC 2023 , Edited by admin on Fri Dec 15 16:22:05 UTC 2023
LIVERTOX NBK548514
Created by admin on Fri Dec 15 16:22:05 UTC 2023 , Edited by admin on Fri Dec 15 16:22:05 UTC 2023
WHO-ATC J05AR21
Created by admin on Fri Dec 15 16:22:05 UTC 2023 , Edited by admin on Fri Dec 15 16:22:05 UTC 2023
WHO-VATC QJ05AR08
Created by admin on Fri Dec 15 16:22:05 UTC 2023 , Edited by admin on Fri Dec 15 16:22:05 UTC 2023
Code System Code Type Description
CHEBI
68602
Created by admin on Fri Dec 15 16:22:05 UTC 2023 , Edited by admin on Fri Dec 15 16:22:05 UTC 2023
PRIMARY
NCI_THESAURUS
C76929
Created by admin on Fri Dec 15 16:22:05 UTC 2023 , Edited by admin on Fri Dec 15 16:22:05 UTC 2023
PRIMARY
INN
8469
Created by admin on Fri Dec 15 16:22:05 UTC 2023 , Edited by admin on Fri Dec 15 16:22:05 UTC 2023
PRIMARY
PUBCHEM
6451164
Created by admin on Fri Dec 15 16:22:05 UTC 2023 , Edited by admin on Fri Dec 15 16:22:05 UTC 2023
PRIMARY
CAS
500287-72-9
Created by admin on Fri Dec 15 16:22:05 UTC 2023 , Edited by admin on Fri Dec 15 16:22:05 UTC 2023
PRIMARY
DRUG BANK
DB08864
Created by admin on Fri Dec 15 16:22:05 UTC 2023 , Edited by admin on Fri Dec 15 16:22:05 UTC 2023
PRIMARY
HSDB
8153
Created by admin on Fri Dec 15 16:22:05 UTC 2023 , Edited by admin on Fri Dec 15 16:22:05 UTC 2023
PRIMARY
MERCK INDEX
m9619
Created by admin on Fri Dec 15 16:22:05 UTC 2023 , Edited by admin on Fri Dec 15 16:22:05 UTC 2023
PRIMARY Merck Index
USAN
WW-86
Created by admin on Fri Dec 15 16:22:05 UTC 2023 , Edited by admin on Fri Dec 15 16:22:05 UTC 2023
PRIMARY
EVMPD
SUB31456
Created by admin on Fri Dec 15 16:22:05 UTC 2023 , Edited by admin on Fri Dec 15 16:22:05 UTC 2023
PRIMARY
SMS_ID
100000124141
Created by admin on Fri Dec 15 16:22:05 UTC 2023 , Edited by admin on Fri Dec 15 16:22:05 UTC 2023
PRIMARY
RXCUI
1102270
Created by admin on Fri Dec 15 16:22:05 UTC 2023 , Edited by admin on Fri Dec 15 16:22:05 UTC 2023
PRIMARY RxNorm
EPA CompTox
DTXSID10198189
Created by admin on Fri Dec 15 16:22:05 UTC 2023 , Edited by admin on Fri Dec 15 16:22:05 UTC 2023
PRIMARY
DAILYMED
FI96A8X663
Created by admin on Fri Dec 15 16:22:05 UTC 2023 , Edited by admin on Fri Dec 15 16:22:05 UTC 2023
PRIMARY
WIKIPEDIA
RILPIVIRINE
Created by admin on Fri Dec 15 16:22:05 UTC 2023 , Edited by admin on Fri Dec 15 16:22:05 UTC 2023
PRIMARY
LACTMED
Rilpivirine
Created by admin on Fri Dec 15 16:22:05 UTC 2023 , Edited by admin on Fri Dec 15 16:22:05 UTC 2023
PRIMARY
CHEBI
68606
Created by admin on Fri Dec 15 16:22:05 UTC 2023 , Edited by admin on Fri Dec 15 16:22:05 UTC 2023
PRIMARY
ChEMBL
CHEMBL175691
Created by admin on Fri Dec 15 16:22:05 UTC 2023 , Edited by admin on Fri Dec 15 16:22:05 UTC 2023
PRIMARY
DRUG CENTRAL
4174
Created by admin on Fri Dec 15 16:22:05 UTC 2023 , Edited by admin on Fri Dec 15 16:22:05 UTC 2023
PRIMARY
FDA UNII
FI96A8X663
Created by admin on Fri Dec 15 16:22:05 UTC 2023 , Edited by admin on Fri Dec 15 16:22:05 UTC 2023
PRIMARY
ACTIVE MOIETY
Structure of RILPIVIRINE
METABOLITE (PARENT)
Structure of 5-HYDROXY-RILPIVIRINE
SALT/SOLVATE (PARENT)
Structure of RILPIVIRINE HYDROCHLORIDE
NIH
NCATS
PRIVACY ACT
ACCESSIBILITY
DISCLAIMER
HHS VULNERABILITY DISCLOSURE
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