Cenicriviroc
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Also known as TAK-652TBR-652
Summary
Cenicriviroc (CHEMBL2110727) is a phase-3 clinical-stage small-molecule chemokine receptor 5 antagonist targeting CCR5; indicated across 8 conditions including metabolic dysfunction-associated steatohepatitis and metabolic dysfunction-associated steatotic liver disease.
At a glance
- Status: Max clinical phase 3 (not approved)
- Modality: Small molecule
- Targets: 1 (CCR5)
- Indications: 8 conditions
- Clinical trials: 15
- Chemistry: 696.9 Da · C41H52N4O4S
Identifiers
Drug identity and classification
| Field | Value |
|---|---|
| ChEMBL ID | CHEMBL2110727 |
| Name | Cenicriviroc |
| Type | Small molecule |
| Max phase | 3 |
| FDA approved | no |
| PubChem CID | 11285792 |
| ChEBI | CHEBI:149636 |
| Molecular formula | C41H52N4O4S |
| Molecular weight | 696.9 |
| InChIKey | PNDKCRDVVKJPKG-WHERJAGFSA-N |
SMILES: CCCCOCCOC1=CC=C(C=C1)C2=CC/3=C(C=C2)N(CCC/C(=C3)/C(=O)NC4=CC=C(C=C4)[S@@](=O)CC5=CN=CN5CCC)CC(C)C
IUPAC name: (5E)-8-[4-(2-butoxyethoxy)phenyl]-1-(2-methylpropyl)-N-[4-[(S)-(3-propylimidazol-4-yl)methylsulfinyl]phenyl]-3,4-dihydro-2H-1-benzazocine-5-carboxamide
ChEBI definition: A member of the class of benzazocines that is (5Z)-1,2,3,4-tetrahydro-1-benzazocine which is substituted by a 2-methylpropyl, N-{4-[(S)-(1-propyl-1H-imidazol-5-yl)methanesulfinyl]phenyl}carboxamide and 4-(2-butoxyethoxy)phenyl groups at positions 1, 5 and 8, respectively. It is a potent chemokine 2 and 5 receptor antagonist currently in development for the treatment of liver fibrosis in adults with nonalcoholic steatohepatitis (NASH).
Pharmacological roles (ChEBI): chemokine receptor 5 antagonist, anti-HIV agent, chemokine receptor 2 antagonist, antirheumatic drug, anti-inflammatory agent, antifibrotic agent.
Also known as: Cenicriviroc, TAK-652, TBR-652, CENICRIVIROC
Parent form; salt/anhydrous children: CHEMBL2105686
Patent coverage: 729 distinct patent families (2,137 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 2,074 (97%) 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
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 |
|---|---|---|---|---|---|
| CCR5 | CCR5 | Antagonist | 8.6 | 0.7% | P51681 |
Broader ChEMBL bioactivity targets: 4 (assay-derived). Sample: C-C chemokine receptor type 5, C-C chemokine receptor type 5, C-C chemokine receptor type 2, C-C chemokine receptor type 7.
Bioactivity
ChEMBL activities: 5 potent at pChembl ≥ 5 of 5 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):
| Target | pChembl | Type | Value | Unit | Activity ID |
|---|---|---|---|---|---|
| P51682 | 9.6 | IC50 | 0.25 | nM | CHEMBL_ACT_18393158 |
| CCR5 | 8.52 | IC50 | 3 | nM | CHEMBL_ACT_12149722 |
| CCR7 | 8.51 | IC50 | 3.1 | nM | CHEMBL_ACT_19005400 |
| CCR2 | 8.23 | IC50 | 5.9 | nM | CHEMBL_ACT_12149721 |
| CCR2 | 8.23 | IC50 | 5.9 | nM | CHEMBL_ACT_19005399 |
Target pathways
Aggregated over 1 target gene(s): CCR5.
Top Reactome pathways
19 total, by targets touching each:
| Pathway | Targets | Genes |
|---|---|---|
| Cytokine Signaling in Immune system | 1 | CCR5 |
| Signal Transduction | 1 | CCR5 |
| HIV Life Cycle | 1 | CCR5 |
| Early Phase of HIV Life Cycle | 1 | CCR5 |
| HIV Infection | 1 | CCR5 |
| Disease | 1 | CCR5 |
| Immune System | 1 | CCR5 |
| Binding and entry of HIV virion | 1 | CCR5 |
| Signaling by GPCR | 1 | CCR5 |
| Class A/1 (Rhodopsin-like receptors) | 1 | CCR5 |
| Peptide ligand-binding receptors | 1 | CCR5 |
| Chemokine receptors bind chemokines | 1 | CCR5 |
| GPCR downstream signalling | 1 | CCR5 |
| G alpha (i) signalling events | 1 | CCR5 |
| Signaling by Interleukins | 1 | CCR5 |
| GPCR ligand binding | 1 | CCR5 |
| Infectious disease | 1 | CCR5 |
| Interleukin-10 signaling | 1 | CCR5 |
| Viral Infection Pathways | 1 | CCR5 |
Dominant GO biological processes
| GO term | Targets |
|---|---|
| MAPK cascade | 1 |
| dendritic cell chemotaxis | 1 |
| calcium ion transport | 1 |
| apoptotic process | 1 |
| chemotaxis | 1 |
| inflammatory response | 1 |
| immune response | 1 |
| cellular defense response | 1 |
| cell surface receptor signaling pathway | 1 |
| G protein-coupled receptor signaling pathway | 1 |
| positive regulation of cytosolic calcium ion concentration | 1 |
| cell-cell signaling | 1 |
| release of sequestered calcium ion into cytosol by sarcoplasmic reticulum | 1 |
| calcium-mediated signaling | 1 |
| signaling | 1 |
Indications & clinical
Indications
8 indications (0 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 |
|---|---|---|---|
| metabolic dysfunction-associated steatohepatitis | 3 | MONDO:0007027 | EFO:1001249 |
| metabolic dysfunction-associated steatotic liver disease | 3 | MONDO:0013209 | EFO:0003095 |
| severe acute respiratory syndrome | 3 | MONDO:0005091 | MONDO:0100096 |
| HIV infectious disease | 2 | MONDO:0005109 | EFO:0000180 |
| sclerosing cholangitis | 2 | MONDO:0018646 | EFO:0004268 |
| liver disorder | 1 | MONDO:0005154 | EFO:0001421 |
2 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.
Clinical trials
Total trials: 15.
Phase distribution
| Phase | Trials |
|---|---|
| PHASE2 | 9 |
| PHASE1 | 4 |
| PHASE3 | 1 |
| PHASE1/PHASE2 | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT03028740 | PHASE3 | TERMINATED | AURORA: A Study for the Efficacy and Safety of Cenicriviroc (CVC) for the Treatment of Liver Fibrosis in Adults With Nonalcoholic Steatohepatitis (NASH) |
| NCT04488081 | PHASE2 | ACTIVE_NOT_RECRUITING | I-SPY COVID-19 TRIAL: An Adaptive Platform Trial for Critically Ill Patients |
| NCT01092104 | PHASE1/PHASE2 | COMPLETED | A Proof of Concept Study to Evaluate the Antiviral Activity, Safety, and Pharmacokinetics of the CCR5 Antagonist TBR 652 in HIV 1-Infected, Antiretroviral Treatment-Experienced, CCR5 Antagonist-Naïve Patients |
| NCT01338883 | PHASE2 | COMPLETED | Efficacy, Safety, and Tolerability of Cenicriviroc (CVC) in Combination With Truvada or Sustiva Plus Truvada in HIV 1-infected, Antiretroviral Treatment-naïve, Adult Patients Infected With Only CCR5-tropic Virus |
| NCT02128828 | PHASE2 | COMPLETED | Effect of Cenicriviroc on HIV Neurocognitive Impairment |
| NCT02217475 | PHASE2 | COMPLETED | Efficacy and Safety Study of Cenicriviroc for the Treatment of Nonalcoholic Steatohepatitis (NASH) in Adult Participants With Liver Fibrosis |
| NCT02330549 | PHASE2 | COMPLETED | ORION: Effects of Cenicriviroc on Insulin Sensitivity in Subjects With Prediabetes or Type 2 Diabetes Mellitus (T2DM) and Suspected NAFLD |
| NCT02653625 | PHASE2 | COMPLETED | PERSEUS: Preliminary Efficacy and Safety of Cenicriviroc in Adult Participants With Primary Sclerosing Cholangitis |
| NCT03059446 | PHASE2 | TERMINATED | Rollover Study of Cenicriviroc for the Treatment of Liver Fibrosis in Participants With Nonalcoholic Steatohepatitis |
| NCT03517540 | PHASE2 | COMPLETED | Study of Safety, Tolerability, and Efficacy of a Combination Treatment of LJN452 and CVC in Adult Patients With NASH and Liver Fibrosis |
| NCT04500418 | PHASE2 | TERMINATED | Charité Trial of Cenicriviroc (CVC) Treatment for COVID-19 Patients |
| NCT01827540 | PHASE1 | COMPLETED | Study of Dolutegravir (DTG) on PK of Cenicriviroc (CVC), and CVC on PK of DTG & on a Single Dose of Midazolam |
| NCT02342067 | PHASE1 | COMPLETED | Pharmacokinetic and Safety Study of Cenicriviroc and Pioglitazone, When Dosed Alone or in Combination |
| NCT02684799 | PHASE1 | COMPLETED | Pharmacokinetic and Safety Study of Cenicriviroc and Acid Reducing Agents When Dosed Alone or in Combination |
| NCT03376841 | PHASE1 | COMPLETED | Impact of Severe Hepatic Impairment on Pharmacokinetics of Cenicriviroc and Its Metabolites |
Clinical evidence (CIViC)
No CIViC predictive evidence (expected for non-precision-medicine drugs).
Pharmacology
Pharmacogenomics
No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.
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.
13 molecules share ≥1 primary target. Top 13 by shared-target count:
| Molecule | Source | Status | Shared targets |
|---|---|---|---|
| ABAMETAPIR | ChEMBL | Phase 4 (approved) | CCR5 |
| DISULFIRAM | ChEMBL | Phase 4 (approved) | CCR5 |
| MARAVIROC | ChEMBL | Phase 4 (approved) | CCR5 |
| TERFENADINE | ChEMBL | Phase 4 (approved) | CCR5 |
| APLAVIROC | ChEMBL | Phase 3 | CCR5 |
| VICRIVIROC | ChEMBL | Phase 3 | CCR5 |
| ANCRIVIROC | ChEMBL | Phase 2 | CCR5 |
| AZD5672 | ChEMBL | Phase 2 | CCR5 |
| BMS-741672 | ChEMBL | Phase 2 | CCR5 |
| BMS-813160 | ChEMBL | Phase 2 | CCR5 |
| INCB-9471 | ChEMBL | Phase 2 | CCR5 |
| JNJ-17166864 CATION | ChEMBL | Phase 2 | CCR5 |
| Mavorixafor | PubChem | Approved | CCR5 |