Aticaprant

Summary

Aticaprant (CHEMBL1921847) is a phase-3 clinical-stage small molecule targeting OPRD1, OPRK1, and OPRM1; indicated across 5 conditions including major depressive disorder and nicotine dependence.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 3 (OPRD1, OPRK1, OPRM1)
• Indications: 5 conditions
• Clinical trials: 14
• Chemistry: 418.5 Da · C26H27FN2O2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL1921847
Name	Aticaprant
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	44129648
Molecular formula	C26H27FN2O2
Molecular weight	418.5
InChIKey	ZHPMYDSXGRRERG-DEOSSOPVSA-N

SMILES: CC1=CC(=CC(=C1)[C@@H]2CCCN2CC3=CC=C(C=C3)OC4=C(C=C(C=C4)C(=O)N)F)C

IUPAC name: 4-[4-[[(2S)-2-(3,5-dimethylphenyl)pyrrolidin-1-yl]methyl]phenoxy]-3-fluorobenzamide

Also known as: Aticaprant, Cerc-501, CERC-501, Jnj-67953964, JSPA-0658, JSPA0658, LY-2456302, Ly2456302, LY2456302, ATICAPRANT

Patent coverage: 66 distinct patent families (150 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 108 (72%) 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
OPRD1	δ receptor	Antagonist	6.81	0.2%	P41143
OPRK1	κ receptor	Antagonist	9.09	0%	P41145
OPRM1	μ receptor	Antagonist	7.62	0%	P35372

Broader ChEMBL bioactivity targets: 3 (assay-derived). Sample: Mu-type opioid receptor, Delta-type opioid receptor, Kappa-type opioid receptor.

Bioactivity

ChEMBL activities: 7 potent at pChembl ≥ 5 of 7 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
OPRK1	9.22	Ki	0.6	nM	CHEMBL_ACT_12646894
OPRK1	9.1	Ki	0.8	nM	CHEMBL_ACT_15157278
OPRK1	9.02	Ki	0.95	nM	CHEMBL_ACT_7946068
OPRM1	7.79	Ki	16.4	nM	CHEMBL_ACT_12646896
OPRM1	7.64	Ki	22.7	nM	CHEMBL_ACT_7946086
OPRD1	6.91	Ki	122	nM	CHEMBL_ACT_12646895
OPRD1	6.78	Ki	166	nM	CHEMBL_ACT_7946104

Target pathways

Aggregated over 3 target gene(s): OPRD1, OPRK1, OPRM1.

Top Reactome pathways

6 total, by targets touching each:

Pathway	Targets	Genes
Peptide ligand-binding receptors	3	OPRD1, OPRK1, OPRM1
G alpha (i) signalling events	3	OPRD1, OPRK1, OPRM1
Interleukin-4 and Interleukin-13 signaling	2	OPRD1, OPRM1
MECP2 regulates neuronal receptors and channels	2	OPRK1, OPRM1
Opioid Signalling	1	OPRM1
G-protein activation	1	OPRM1

Dominant GO biological processes

GO term	Targets
G protein-coupled receptor signaling pathway	3
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	3
phospholipase C-activating G protein-coupled receptor signaling pathway	3
neuropeptide signaling pathway	3
G protein-coupled opioid receptor signaling pathway	3
signal transduction	3
immune response	2
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	2
response to nicotine	2
eating behavior	2
response to ethanol	2
sensory perception	2
sensory perception of pain	2
adult locomotory behavior	1
negative regulation of gene expression	1

Indications & clinical

Indications

5 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
major depressive disorder	3	MONDO:0002009	MONDO:0002009
nicotine dependence	2	MONDO:0008575	EFO:0003768
anxiety	1	MONDO:0011918	EFO:0005230

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

Clinical trials

Total trials: 14.

Phase distribution

Phase	Trials
PHASE3	5
PHASE2	5
PHASE1	4

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05455684	PHASE3	COMPLETED	A Study of Aticaprant as Adjunctive Therapy in Adult Participants With Major Depressive Disorder (MDD) With Moderate-to-severe Anhedonia and Inadequate Response to Current Antidepressant Therapy
NCT05518149	PHASE3	TERMINATED	A Study of Aticaprant in Adult and Elderly Participants With Major Depressive Disorder (MDD)
NCT05550532	PHASE3	COMPLETED	A Study of Aticaprant 10 Milligrams (mg) as Adjunctive Therapy in Adult Participants With MDD With Moderate-to-severe Anhedonia and Inadequate Response to Current Antidepressant Therapy
NCT06514742	PHASE3	TERMINATED	A Study of Aticaprant 10 mg as Adjunctive Therapy in Adult Participants With Major Depressive Disorder (MDD) With Moderate-to-severe Anhedonia and Inadequate Response to Current Antidepressant Therapy and Long-term Extension Treatment With Aticaprant
NCT06635135	PHASE3	TERMINATED	A Study of Aticaprant Plus an Antidepressant to Prevent Return of Depression Symptoms in Participants With Major Depressive Disorder Who Experience a Loss of Interest and Pleasure
NCT01913535	PHASE2	TERMINATED	Proof-of-Concept Trial of CERC-501 Augmentation of Antidepressant Therapy in Treatment-Resistant Depression
NCT02218736	PHASE2	COMPLETED	Fast-Fail Trials in Mood and Anxiety Spectrum Disorders; Kappa Opioid Receptor Phase 2a
NCT02641028	PHASE2	COMPLETED	A Study in a Human Laboratory Model of Smoking Behavior
NCT02800928	PHASE2	COMPLETED	Does CERC-501 Attenuate Stress-precipitated Smoking Lapse?
NCT03559192	PHASE2	COMPLETED	A Study to Explore the Efficacy of JNJ-67953964 in the Treatment of Depression
NCT07615426	PHASE1	RECRUITING	A Study of the Feasibility, Safety and Tolerability of Aticaprant as Adjunctive Treatment in Participants With Schizophrenia
NCT02218775	PHASE1	WITHDRAWN	FASTMAS (Fast-Fail Trials in Mood and Anxiety Spectrum Disorders) Kappa Opioid Receptor Phase 1 Study
NCT04185051	PHASE1	COMPLETED	A Study to Investigate the Effect of JNJ-67953964 on Gastric Mucosal Integrity in Healthy Male and Female Participants
NCT04791332	PHASE1	COMPLETED	A Study of JNJ-67953964 in Healthy Japanese Adult Male Participants

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

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.

612 molecules share ≥1 primary target. Top 60 by shared-target count:

Molecule	Source	Status	Shared targets
Dihydroergotamine	ChEMBL + PubChem	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
PROPOXYPHENE	ChEMBL + PubChem	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
TAFAMIDIS	ChEMBL + PubChem	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
ALVIMOPAN	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
AMIODARONE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
AMLODIPINE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
AMOXAPINE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
BENZTROPINE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
BUPRENORPHINE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
BUTORPHANOL	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
CANDESARTAN CILEXETIL	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
CANNABIDIOL	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
CHLORPROMAZINE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
CINNARIZINE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
CLOTRIMAZOLE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
CODEINE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
DIETHYLSTILBESTROL	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
ECONAZOLE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
FENTANYL	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
FLUPHENAZINE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
FLUSPIRILENE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
HYDROCODONE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
HYDROMORPHONE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
LANSOPRAZOLE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
LEVORPHANOL	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
LOPERAMIDE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
LOXAPINE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
MEPERIDINE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
METHADONE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
METHYLNALTREXONE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
MICONAZOLE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
MORPHINE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
NAFTOPIDIL	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
NALBUPHINE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
NALFURAFINE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
NALMEFENE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
NALOXONE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
NALTREXONE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
NELFINAVIR	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
OLICERIDINE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
OXYCODONE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
OXYMORPHONE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
PAROXETINE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
PASIREOTIDE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
PENTAZOCINE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
PIMOZIDE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
RALOXIFENE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
RITONAVIR	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
SAMIDORPHAN	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
SAQUINAVIR	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
SUNITINIB	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
TAMOXIFEN	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
TRAMADOL	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
ASIMADOLINE	ChEMBL	Phase 3	OPRD1, OPRK1, OPRM1
CEBRANOPADOL	ChEMBL	Phase 3	OPRD1, OPRK1, OPRM1
NAVACAPRANT	ChEMBL	Phase 3	OPRD1, OPRK1, OPRM1
TRIMEBUTINE	ChEMBL	Phase 3	OPRD1, OPRK1, OPRM1
BREMAZOCINE	ChEMBL	Phase 2	OPRD1, OPRK1, OPRM1
CARFENTANIL	ChEMBL	Phase 2	OPRD1, OPRK1, OPRM1