Rilpivirine

Summary

Rilpivirine (CHEMBL175691) is an approved small-molecule HIV-1 reverse transcriptase inhibitor (ATC J05AG05); 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: J05AG05
• Indications: 6 conditions
• Clinical trials: 62
• Chemistry: 366.4 Da · C22H18N6

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL175691
Name	Rilpivirine
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	6451164
ChEBI	CHEBI:68606
ATC	J05AG05
Molecular formula	C22H18N6
Molecular weight	366.4
InChIKey	YIBOMRUWOWDFLG-ONEGZZNKSA-N

SMILES: CC1=CC(=CC(=C1NC2=NC(=NC=C2)NC3=CC=C(C=C3)C#N)C)/C=C/C#N

IUPAC name: 4-[[4-[4-[(E)-2-cyanoethenyl]-2,6-dimethylanilino]pyrimidin-2-yl]amino]benzonitrile

ChEBI definition: An aminopyrimidine that is pyrimidine-2,4-diamine in which the amino groups at positions 2 and 4 are substituted by 4-cyanophenyl and 4-[(E)-2-cyanovinyl]-2,6-dimethylphenyl groups respectively. Used for treatment of HIV.

Pharmacological roles (ChEBI): HIV-1 reverse transcriptase inhibitor, EC 2.7.7.49 (RNA-directed DNA polymerase) inhibitor.

Also known as: Edurant, R 278474, R-278474, R278474, Rekambys, Rilpivirina, Rilpivirine, Rilpivirine component of cabenuva, TMC-278, TMC278, RILPIVIRINE, rilpivirine

Parent form; salt/anhydrous children: CHEMBL1628504, CHEMBL6142599, CHEMBL6169905

Patent coverage: 1,457 distinct patent families (3,706 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 3,296 (89%) of the total. 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: 7 (assay-derived). Sample: Voltage-gated inwardly rectifying potassium channel KCNH2, Cytochrome P450 2D6, Cytochrome P450 1A2, Cytochrome P450 2C9, Cytochrome P450 3A4, Cytochrome P450 2C19, Broad substrate specificity ATP-binding cassette transporter ABCG2.

Bioactivity

ChEMBL activities: 66 potent at pChembl ≥ 5 of 66 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
CYP2C19	6.47	IC50	335	nM	CHEMBL_ACT_19063364
CYP2C19	6.47	IC50	335	nM	CHEMBL_ACT_23259667
CYP2C19	6.47	IC50	335	nM	CHEMBL_ACT_24356370
CYP2C19	6.47	IC50	335	nM	CHEMBL_ACT_24740406
CYP2C19	6.47	IC50	340	nM	CHEMBL_ACT_24822365
CYP2C19	6.47	IC50	335	nM	CHEMBL_ACT_25502130
CYP2C19	6.47	IC50	335	nM	CHEMBL_ACT_25508210
CYP2C19	6.47	IC50	335	nM	CHEMBL_ACT_26142478
CYP2C19	6.47	IC50	335	nM	CHEMBL_ACT_29080906
CYP2C19	6.47	IC50	335	nM	CHEMBL_ACT_29097777
CYP2C19	6.47	IC50	340	nM	CHEMBL_ACT_29257278
CYP2C9	6.46	IC50	346	nM	CHEMBL_ACT_19063368
CYP2C9	6.46	IC50	346	nM	CHEMBL_ACT_23259664
CYP2C9	6.46	IC50	346	nM	CHEMBL_ACT_24356367
CYP2C9	6.46	IC50	346	nM	CHEMBL_ACT_24740403
CYP2C9	6.46	IC50	350	nM	CHEMBL_ACT_24822361
CYP2C9	6.46	IC50	346	nM	CHEMBL_ACT_25502127
CYP2C9	6.46	IC50	346	nM	CHEMBL_ACT_25508206
CYP2C9	6.46	IC50	346	nM	CHEMBL_ACT_26142474
CYP2C9	6.46	IC50	346	nM	CHEMBL_ACT_29080909
CYP2C9	6.46	IC50	346	nM	CHEMBL_ACT_29097769
CYP2C9	6.46	IC50	350	nM	CHEMBL_ACT_29257275
KCNH2	6.3	IC50	500	nM	CHEMBL_ACT_19063661
KCNH2	6.3	IC50	500	nM	CHEMBL_ACT_19156559
KCNH2	6.3	IC50	500	nM	CHEMBL_ACT_23259685
KCNH2	6.3	IC50	500	nM	CHEMBL_ACT_24807885
KCNH2	6.3	IC50	500	nM	CHEMBL_ACT_24822408
KCNH2	6.3	IC50	500	nM	CHEMBL_ACT_25502154
KCNH2	6.3	IC50	500	nM	CHEMBL_ACT_25508222
KCNH2	6.3	IC50	500	nM	CHEMBL_ACT_25593415

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	3	MONDO:0012268	EFO:0000765
hepatitis C virus infection	1	MONDO:0005231	EFO:0003047

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

Clinical trials

Total trials: 62.

Phase distribution

Phase	Trials
PHASE1	17
PHASE3	12
PHASE4	11
PHASE2	9
Not specified	9
PHASE2/PHASE3	2
PHASE1/PHASE2	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01585038	PHASE4	COMPLETED	Efavirenz Versus Rilpivirine on Vascular Function, Inflammation, and Oxidative Stress
NCT01715636	PHASE4	COMPLETED	Safety, Tolerability,and Adherence to Co-formulated Tenofovir-emtricitabine-rilpivirine Used as HIV Nonoccupational Post-exposure Prophylaxis in Men Who Have Sex With Men.
NCT01736761	PHASE4	COMPLETED	A Phase IV, Open-label Single-arm Study Investigating the Pharmacokinetics and Pharmacodynamics of the Antiretroviral Combination of Rilpivirine and Ritonavirboosted Darunavir in Therapy-naive HIV-1 Infected Patients.
NCT01777997	PHASE4	COMPLETED	FTC/RPV/TDF on T-Cell Activation, CD4+ T-Cell Count, Inflammatory Biomarkers and Viral Reservoir
NCT01804244	PHASE4	COMPLETED	A Single-Dose Pharmacokinetics and Safety Study of TMC278 in Healthy Adult Japanese Participants
NCT02404233	PHASE4	UNKNOWN	Open Label, Pilot Study of Darunavir Boosted by Cobicistat in Combination With Rilpivirine to Treat HIV+ Naïve Subjects
NCT02447016	PHASE4	TERMINATED	Decrease of Neuropsychiatric Side Effects After Switching From Atripla to Eviplera
NCT02470650	PHASE4	WITHDRAWN	Cost-effectiveness of Different Antiretroviral Treatment in Patients HIV Naive
NCT02530060	PHASE4	COMPLETED	A Study to Evaluate the Pharmacokinetics of Rilpivirine/Tenofovir/Emtricitabine After a Single-Oral Administration in Healthy Japanese Adult Male Participants
NCT02547844	PHASE4	COMPLETED	Evolution of Plasma Lipid Profile in Patients With HIV1 Who Change Atripla to Eviplera Compared to Continue With Atripla
NCT03567304	PHASE4	UNKNOWN	Neurocognitive Function Improvement After Switching From Efavirenz to Rilpivirine
NCT03299049	PHASE3	ACTIVE_NOT_RECRUITING	Efficacy, Safety and Tolerability Study of Long-acting Cabotegravir Plus Long-acting Rilpivirine (CAB LA + RPV LA) in Human-immunodeficiency Virus-1 (HIV-1) Infected Adults
NCT05546242	PHASE3	ACTIVE_NOT_RECRUITING	Improving HIV-1 Control in Africa with Long Acting Antiretrovirals
NCT06507059	PHASE3	RECRUITING	Outcomes of the PLHIV With Suboptimal Viral Suppression to Injectable Long-acting Antiretrovirals
NCT00540449	PHASE3	COMPLETED	TMC278-TiDP6-C209: A Clinical Trial in Treatment Naive HIV-1 Patients Comparing TMC278 to Efavirenz in Combination With Tenofovir + Emtricitabine.
NCT00543725	PHASE3	COMPLETED	TMC278-TiDP6-C215: A Clinical Trial in Treatment Naive HIV-subjects Patients Comparing TMC278 to Efavirenz in Combination With 2 Nucleoside/Nucleotide Reverse Transcriptase Inhibitors
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
NCT01266902	PHASE3	COMPLETED	A Trial With TMC278-TIDP6-C222 for Continued TMC278 Access in Patients Infected With Human Immunodeficiency Virus-1
NCT01701882	PHASE3	COMPLETED	A Pilot Study to Assess the Feasibility of Switching, Individuals Receiving Atripla With Continuing Central Nervous System (CNS) Toxicity, to a Fixed Dose Combination of Tenofovir/Emtricitabine/Rilpivirine
NCT01709084	PHASE3	COMPLETED	A Clinical Trial Comparing the Efficacy of Tenofovir Disoproxil Fumarate/Emtricitabine/Rilpivirine (TDF/FTC/RPV) Versus TDF/FTC/Efavirenz (TDF/FTC/EFV) in Patients With Undetectable Plasma HIV-1 RNA on Current First-line Treatment
NCT02104700	PHASE2/PHASE3	COMPLETED	Switch From Nevirapine-based Regimen to Once a Day Rilpivirine/Emtricitabine/Tenofovir
NCT03033368	PHASE2/PHASE3	UNKNOWN	Rilpivirine in Virologically Suppressed Adolescents
NCT03563742	PHASE3	TERMINATED	A Study to Determine the Safety and Efficacy of Rilpivirine in Treatment-naive Indian Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Infection
NCT04542070	PHASE3	COMPLETED	A Study to Evaluate Efficacy and Safety of Cabotegravir (CAB) Long Acting (LA) Plus (+) Rilpivirine (RPV) LA Versus BIKTARVY® (BIK) in Participants With Human Immunodeficiency Virus (HIV)-1 Who Are Virologically Suppressed
NCT05349838	PHASE3	COMPLETED	Open-Label Multi-Centre Randomised Switch Study to Evaluate Virological Efficacy Over 96Weeks Of 2-Drug Therapy With Dolutegravir(DTG)/Rilpivirine(RPV) Fixed Dose Combination(FDC) in Antiretroviral Treatment-Experienced HIV-1 Infected Subjects Virologically Suppressed With NNRTI Mutation K103N
NCT02494986	PHASE2	ACTIVE_NOT_RECRUITING	A Roll-over Study With Rilpivirine for Human Immunodeficiency Virus Type 1 (HIV-1) Infected Participants Who Participated in Rilpivirine Pediatric Studies
NCT06411223	PHASE2	ACTIVE_NOT_RECRUITING	Pharmacist-led Intervention for Injectable HIV Treatment for Women With Health-related Social Needs
NCT00110305	PHASE2	COMPLETED	A Study of TMC278 in Human Immunodeficiency Virus Type 1 Infected Patients, Who Are Not Treated With Antiretroviral Medicines
NCT00799864	PHASE2	COMPLETED	A Study to Evaluate the Pharmacokinetics, Safety, Tolerability, and Antiviral Activity of Rilpivirine (TMC278) in Human Immunodeficiency Virus Infected Adolescents and Children Aged Greater Than or Equal to 6 Years
NCT01641809	PHASE2	COMPLETED	Dose Ranging Study of GSK1265744 Plus Nucleoside Reverse Transcriptase Inhibitors for Induction of Human Immunodeficiency Virus-1 (HIV-1) Virologic Suppression Followed by Virologic Suppression Maintenance by GSK1265744 Plus Rilpivirine
NCT01975012	PHASE1/PHASE2	WITHDRAWN	Safety, Tolerability, Drug Interactions, and Antiviral Activity of Rilpivirine in Antiretroviral-Naive HIV-Infected Children Less Than 12 Years of Age
NCT02165202	PHASE2	COMPLETED	Phase II Safety and Acceptability of an Investigational Injectable Product, TMC278LA, for Pre-Exposure Prophylaxis
NCT03497676	PHASE1/PHASE2	COMPLETED	More Options for Children and Adolescents (MOCHA): Oral and Long-Acting Injectable Cabotegravir and Rilpivirine in HIV-Infected Children and Adolescents
NCT03589027	PHASE2	UNKNOWN	Darunavir and Rilpivirine Interactions With Levonorgestrel Implant
NCT03589040	PHASE2	UNKNOWN	Darunavir and Rilpivirine Interactions With Etonogestrel Contraceptive Implant
NCT04012931	PHASE2	COMPLETED	A Study of Switching to RPV Plus Other ARVs in HIV-1-infected Children (Aged 2 to <12 Years) Who Are Virologically Suppressed
NCT00736905	PHASE1	COMPLETED	TMC278-TiDP6-C130: Pharmacokinetics, Safety and Tolerability of TMC278 in Subjects With Mildly or Moderately Impaired Hepatic Function.
NCT00739622	PHASE1	COMPLETED	TMC278-TiDP6-C136: Effect of TMC278 on Ethinylestradiol and Norethindrone in Healthy Women.
NCT00741741	PHASE1	TERMINATED	TMC278-TiDP15-C150: Trial to Examine Safety, Tolerability and Plasma Pharmacokinetics of Multiple Doses of TMC278LA.
NCT00744770	PHASE1	COMPLETED	TMC278-TiDP6-C121: Drug-drug Interaction Trial to Investigate the Potential Interaction Between TMC278 25 mg Daily and Methadone, at Steady State.

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 0 clinical and 3 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).