DAPIVIRINE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C20H19N5
Molecular Weight	329.3984
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1=CC(C)=C(NC2=NC(NC3=CC=C(C=C3)C#N)=NC=C2)C(C)=C1

InChI

InChIKey=ILAYIAGXTHKHNT-UHFFFAOYSA-N

InChI=1S/C20H19N5/c1-13-10-14(2)19(15(3)11-13)24-18-8-9-22-20(25-18)23-17-6-4-16(12-21)5-7-17/h4-11H,1-3H3,(H2,22,23,24,25)

HIDE SMILES / InChI

Molecular Formula	C20H19N5
Molecular Weight	329.3984
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://www.ipmglobal.org/our-work/arvs-in-the-pipeline/dapivirine-tmc120
Curator's Comment: Description was created using several sources including: http://www.mtnstopshiv.org/news/studies/mtn020 | https://www.ncbi.nlm.nih.gov/pubmed/14693562 | https://clinicaltrials.gov/ct2/show/NCT02010593

Dapivirine, an anti-retroviral (ARV)-based microbicide, is a substituted diaminopyrimidine (DAPY) derivative and a potent non-nucleoside reverse-transcriptase inhibitor (NNRTI) with antiviral activity against HIV-1. Dapivirine showed high activity against wild-type and mutant HIV in in virto HIV models inhibiting a broad panel of HIV-1 isolates from different classes, including a wide range of NNRTI-resistant isolates. Developed by Janssen Sciences (formerly Tibotec Pharmaceuticals), dapivirine was initially tested as an oral treatment for HIV in a number of Phase I/II clinical trials. In 2014 the International Partnership for Microbicides (IPM) began its work on the monthly dapivirine ring. Phase I/II clinical trials in Africa, Europe and the United States proved that dapivirine is safe and well-tolerated. Phase III long-term safety and efficacy studies of the monthly dapivirine ring as part of IPM's Dapivirine Ring Licensure Program confirmed that the monthly dapivirine ring can safely help prevent HIV infection in women. In 2016 the ASPIRE Study reported a 27 percent reduction in HIV-1 acquisition with a trend toward greater protection in women over age 21 and no significant protection for women under age 21.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Human immunodeficiency virus type 1 reverse transcriptase 70 Target ID: CHEMBL247 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14693562 \| https://www.ncbi.nlm.nih.gov/pubmed/26510386 \| http://www.mtnstopshiv.org/news/studies/mtn020	Inhibitor 8504		24.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
HIV-1 infection 156 Sources: https://clinicaltrials.gov/ct2/show/NCT02010593	Preventing		Phase II 1147	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
280 pg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/34118115/	25 mg single, vaginal dose: 25 mg route of administration: Vaginal experiment type: SINGLE co-administered:	DAPIVIRINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
487 pg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/34118115/	100 mg single, vaginal dose: 100 mg route of administration: Vaginal experiment type: SINGLE co-administered:	DAPIVIRINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
505 pg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/34118115/	200 mg single, vaginal dose: 200 mg route of administration: Vaginal experiment type: SINGLE co-administered:	DAPIVIRINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
462 pg/mL DRUG LABEL https://www.ema.europa.eu/en/documents/outside-eu-product-information/dapivirine-vaginal-ring-25-mg-product-information_en-0.pdf	25 mg single, vaginal dose: 25 mg route of administration: Vaginal experiment type: SINGLE co-administered:	DAPIVIRINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
91 pg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27809557/	1.25 mg single, vaginal dose: 1.25 mg route of administration: Vaginal experiment type: SINGLE co-administered:	DAPIVIRINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
132 pg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27809557/	1.25 mg single, vaginal dose: 1.25 mg route of administration: Vaginal experiment type: SINGLE co-administered:	DAPIVIRINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
33.249 ng × day/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/34118115/	100 mg single, vaginal dose: 100 mg route of administration: Vaginal experiment type: SINGLE co-administered:	DAPIVIRINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
34.78 ng × day/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/34118115/	200 mg single, vaginal dose: 200 mg route of administration: Vaginal experiment type: SINGLE co-administered:	DAPIVIRINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
229408 pg × h/mL DRUG LABEL https://www.ema.europa.eu/en/documents/outside-eu-product-information/dapivirine-vaginal-ring-25-mg-product-information_en-0.pdf	25 mg single, vaginal dose: 25 mg route of administration: Vaginal experiment type: SINGLE co-administered:	DAPIVIRINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
7952 pg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27809557/	1.25 mg single, vaginal dose: 1.25 mg route of administration: Vaginal experiment type: SINGLE co-administered:	DAPIVIRINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
7832 pg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27809557/	1.25 mg single, vaginal dose: 1.25 mg route of administration: Vaginal experiment type: SINGLE co-administered:	DAPIVIRINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
81.5 h DRUG LABEL https://www.ema.europa.eu/en/documents/outside-eu-product-information/dapivirine-vaginal-ring-25-mg-product-information_en-0.pdf	25 mg single, vaginal dose: 25 mg route of administration: Vaginal experiment type: SINGLE co-administered:	DAPIVIRINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
59 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27809557/	1.25 mg single, vaginal dose: 1.25 mg route of administration: Vaginal experiment type: SINGLE co-administered:	DAPIVIRINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
52 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27809557/	1.25 mg single, vaginal dose: 1.25 mg route of administration: Vaginal experiment type: SINGLE co-administered:	DAPIVIRINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
0.4% DRUG LABEL https://www.ema.europa.eu/en/documents/outside-eu-product-information/dapivirine-vaginal-ring-25-mg-product-information_en-0.pdf	25 mg single, vaginal dose: 25 mg route of administration: Vaginal experiment type: SINGLE co-administered:		DAPIVIRINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
200 mg single, vaginal Highest studied dose Dose: 200 mg Route: vaginal Route: single Dose: 200 mg Sources: https://pubmed.ncbi.nlm.nih.gov/34118115/	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/34118115/	Sources: https://pubmed.ncbi.nlm.nih.gov/34118115/
0.05 % 1 times / day multiple, vaginal Studied dose Dose: 0.05 %, 1 times / day Route: vaginal Route: multiple Dose: 0.05 %, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/26565716/	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/26565716/	Sources: https://pubmed.ncbi.nlm.nih.gov/26565716/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946 inhibitor 2252 inducer 1087	inhibitor 2438	inhibitor 2507

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A1 132 CYP2C19 2057 CYP1B1 32 UGT1A4 98 UGT1A8 37 CYP2B6 926 UGT1A6 136 UGT1A9 148 UGT1A1 246 CYP1A2 2153 CYP2C8 1057 BCRP 910 MRP1 116 UGT1A7 23 UGT2B7 197 UGT1A3 89 MRP4 290 P-gp 1741	UGT1A8 323 CYP2C8 810 CYP1A2 1197 CYP1A1 389 CYP2B6 776 CYP2C19 1119 CYP1B1 104 UGT1A3 470 UGT1A1 479 UGT1A4 399 UGT1A7 249 UGT1A6 343 UGT1A9 423 BCRP 697 MRP1 113 UGT2B7 456 P-gp 2052 MRP4 91	MRP3 83 PEPT2 2 CYP2B6 669 CYP1A2 832 MRP2 146 MRP5 45 OCT3 2 OCT1 39 MRP7 2 GLUT3 2 MRP1 74 GLUT1 14

Drug as perpetrator

Target	Modality	Activity
CYP2C8 1117	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/34959473/	moderate [IC50 1.41 uM]
CYP1B1 93	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/34959473/	moderate [IC50 1.55 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/34959473/	moderate [IC50 4.9 uM]
UGT1A1 303	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/34959473/	moderate [IC50 5.2 uM]
UGT1A4 100	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/34959473/	moderate [IC50 9.45 uM]
MRP3 326	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/26102284/	moderate
BCRP 985	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/36145696/	no
CYP1A2 2333	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/34959473/	no
CYP2B6 1160	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/34959473/	no
CYP3A4 2633	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/34959473/	no
MRP1 232	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/36145696/	no
MRP4 345	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/36145696/	no
P-gp 1932	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/36145696/	no
CYP2B6 1160	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/34959473/	weak [IC50 10.07 uM]
CYP1A2 2333	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/34959473/	weak [IC50 10.53 uM]
UGT1A3 99	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/34959473/	weak [IC50 16.98 uM]
UGT2B7 210	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/34959473/	weak [IC50 17.22 uM]
UGT1A6 171	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/34959473/	weak [IC50 19.59 uM]
UGT1A7 25	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/34959473/	weak [IC50 24.15 uM]
CYP2C19 2141	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/34959473/	weak [IC50 >30 uM]
UGT1A8 49	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/34959473/	weak [IC50 >30 uM]
UGT1A9 155	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/34959473/	weak [IC50 >30 uM]
GLUT1 20	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/26102284/	weak
GLUT3 2	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/26102284/	weak
MRP1 232	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/26102284/	weak
MRP2 625	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/26102284/	weak
MRP5 80	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/26102284/	weak
MRP7 6	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/26102284/	weak
OCT1 656	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/26102284/	weak
OCT3 161	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/26102284/	weak
PEPT2 17	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/26102284/	weak
CYP2D6 2546	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/214347#section=BioAssay-Results Page: 36.0	yes [IC50 10.684 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/214347#section=BioAssay-Results Page: 34.0	yes [IC50 3.7908 uM]
CYP1A1 272	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/34959473/	yes

Drug as victim

Target	Modality	Activity
CYP1A1 389	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/34959473/	major
BCRP 697	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/36145696/	no
CYP1A2 1197	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/34959473/	no
CYP1B1 104	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/34959473/	no
CYP2B6 776	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/34959473/	no
CYP2C19 1119	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/34959473/	no
CYP2C8 810	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/34959473/	no
MRP1 113	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/36145696/	no
MRP4 91	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/36145696/	no
P-gp 2052	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/36145696/	no
UGT1A1 479	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/34959473/	no
UGT1A3 470	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/34959473/	no
UGT1A4 399	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/34959473/	no
UGT1A6 343	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/34959473/	no
UGT1A7 249	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/34959473/	no
UGT1A8 323	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/34959473/	no
UGT1A9 423	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/34959473/	no
UGT2B7 456	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/34959473/	no
CYP3A4 1946	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/34959473/	yes

PubMed

Title	Date	PubMed
Optimization of diarylazines as anti-HIV agents with dramatically enhanced solubility.	2013-09-15	23937980
Synthesis, evaluation and structure-activity relationships of triazine dimers as novel antiviral agents.	2012-12-01	23084903
Novel diarylpyridinones, diarylpyridazinones and diarylphthalazinones as potential HIV-1 nonnucleoside reverse transcriptase inhibitors (NNRTIs).	2011-10-15	21930388
Synergy against drug-resistant HIV-1 with the microbicide antiretrovirals, dapivirine and tenofovir, in combination.	2011-08-24	21633286
Complete inactivation of HIV-1 using photo-labeled non-nucleoside reverse transcriptase inhibitors.	2011-01	20937333
Selective killing of human immunodeficiency virus infected cells by non-nucleoside reverse transcriptase inhibitor-induced activation of HIV protease.	2010-10-15	20950436
Inhibition of HIV-1 by non-nucleoside reverse transcriptase inhibitors via an induced fit mechanism-Importance of slow dissociation and relaxation rates for antiviral efficacy.	2010-10-15	20599774
Inhibition of human immunodeficiency virus type 1 infection by the candidate microbicide dapivirine, a nonnucleoside reverse transcriptase inhibitor.	2009-02	19029331
Potent nonnucleoside reverse transcriptase inhibitors target HIV-1 Gag-Pol.	2006-11	17096588
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).	2005-03-24	15771434
TMC125, a novel next-generation nonnucleoside reverse transcriptase inhibitor active against nonnucleoside reverse transcriptase inhibitor-resistant human immunodeficiency virus type 1.	2004-12	15561844
A series of diaryltriazines and diarylpyrimidines are highly potent nonnucleoside reverse transcriptase inhibitors with possible applications as microbicides.	2004-10	15388420
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.	2004-05-06	15115397
In vitro evaluation of nonnucleoside reverse transcriptase inhibitors UC-781 and TMC120-R147681 as human immunodeficiency virus microbicides.	2004-01	14693562
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	15357624

Patents

Sample Use Guides

In Vivo Use Guide

The dapivirine matrix vaginal ring containing 25 mg of drug substance dispersed in a platinum-catalyzed-cured silicone matrix inserts once every 4 weeks in postmenopausal women over 12 weeks of product use.

Route of Administration: Other

In Vitro Use Guide

A 24-h treatment with 100 nM TMC120-R147681 (dapivirine) prevented cell-free HIV infection, whereas 10-fold-higher concentrations blocked cell-associated HIV when studied using monocyte-derived dendritic cells (MO-DC) and autologous CD4+ T cells, representing early targets during sexual transmission.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:33:15 GMT 2025` Edited by `admin` on `Mon Mar 31 18:33:15 GMT 2025`
Record UNII	TCN4MG2VXS
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

AIDS-105293

Preferred Name

English

DAPIVIRINE

Official Name

English

4-({4-[(2,4,6-Trimethylphenyl)amino]pyrimidin-2-yl}amino)benzonitrile

Systematic Name

English

DAPIVIRINE [USAN]

Common Name

English

R-147681

Code

English

Dapivirine [WHO-DD]

Common Name

English

GEL-02

Common Name

English

dapivirine [INN]

Common Name

English

TMC120

Common Name

English

TMC-120

Code

English

Classification Tree Code System Code

WHO-ATC

G01AX17