Navacaprant

Summary

Navacaprant (CHEMBL4592045) is a phase-3 clinical-stage small molecule targeting OPRD1, OPRK1, and OPRM1; indicated across 2 conditions including major depressive disorder.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 3 (OPRD1, OPRK1, OPRM1)
• Indications: 2 conditions
• Clinical trials: 6
• Chemistry: 453.6 Da · C25H32FN5O2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL4592045
Name	Navacaprant
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	137434175
Molecular formula	C25H32FN5O2
Molecular weight	453.6
InChIKey	CQOJHAJWCDJEAT-UHFFFAOYSA-N

SMILES: CCC1=CC2=C(C(=C(N=C2C(=C1)F)N3CCC(CC3)NC4CCOCC4)C5=NC(=NO5)C)C

IUPAC name: 1-[6-ethyl-8-fluoro-4-methyl-3-(3-methyl-1,2,4-oxadiazol-5-yl)quinolin-2-yl]-N-(oxan-4-yl)piperidin-4-amine

Also known as: BTRX-140, Btrx-335140, BTRX-335140, BTRX335140, CYM-53093, CYM53093, Navacaprant, NMRA-140, Nmra-335140, NMRA-335140, NMRA335140, NAVACAPRANT

Parent form; salt/anhydrous children: CHEMBL4455146, CHEMBL6068414

Patent coverage: 26 distinct patent families (39 SureChEMBL compound mentions), from 6 matched compound structure(s). One matched structure accounts for 28 (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	5.19	0.2%	P41143
OPRK1	κ receptor	Antagonist	9.1	0%	P41145
OPRM1	μ receptor	Antagonist	6.96	0%	P35372

Broader ChEMBL bioactivity targets: 4 (assay-derived). Sample: Mu-type opioid receptor, Delta-type opioid receptor, Kappa-type opioid receptor, Voltage-gated inwardly rectifying potassium channel KCNH2.

Bioactivity

ChEMBL activities: 9 potent at pChembl ≥ 5 of 9 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
OPRK1	9.1	IC50	0.8	nM	CHEMBL_ACT_19368156
KCNH2	9	IC50	1	nM	CHEMBL_ACT_19368131
OPRK1	8.82	Ki	1.5	nM	CHEMBL_ACT_19368491
OPRM1	6.96	IC50	110	nM	CHEMBL_ACT_19368182
OPRK1	6.39	EC50	410	nM	CHEMBL_ACT_25611629
OPRM1	6.35	Ki	450	nM	CHEMBL_ACT_19368492
OPRM1	6.26	IC50	550	nM	CHEMBL_ACT_28504172
OPRM1	5.34	EC50	4590	nM	CHEMBL_ACT_25611630
OPRD1	5.19	IC50	6500	nM	CHEMBL_ACT_19368208

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

2 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

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

Clinical trials

Total trials: 6.

Phase distribution

Phase	Trials
PHASE3	4
PHASE2	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06029439	PHASE3	RECRUITING	Study to Assess the Safety and Effectiveness of NMRA-335140-501
NCT06058013	PHASE3	ACTIVE_NOT_RECRUITING	Study to Assess the Effects of Oral NMRA-335140 Versus Placebo in Participants With Major Depressive Disorder
NCT06058039	PHASE3	ACTIVE_NOT_RECRUITING	Study to Assess the Effects of Oral NMRA-335140 in Participants With Major Depressive Disorder
NCT06029426	PHASE3	COMPLETED	Study to Evaluate the Effects of Oral NMRA-335140 Versus Placebo in Participants With Major Depressive Disorder
NCT04221230	PHASE2	COMPLETED	Study in Major Depressive Disorder With NMRA-335140 (BTRX-335140) vs Placebo
NCT06429722	PHASE2	COMPLETED	To Evaluate the Effects of NMRA-335140 on Symptoms of Major Depression in Participants With Bipolar II Disorder.

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
ATICAPRANT	ChEMBL	Phase 3	OPRD1, OPRK1, OPRM1
CEBRANOPADOL	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