Crinecerfont

Summary

Crinecerfont (CHEMBL291657) is an approved small molecule targeting CRHR1; indicated across 2 conditions including congenital adrenal hyperplasia and depressive disorder.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• Targets: 1 (CRHR1)
• Indications: 2 conditions
• Clinical trials: 7
• Chemistry: 483 Da · C27H28ClFN2OS

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL291657
Name	Crinecerfont
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	5282340
Molecular formula	C27H28ClFN2OS
Molecular weight	483
InChIKey	IEAKXXNRGSLYTQ-DEOSSOPVSA-N

SMILES: CC1=C(C=C(C=C1)[C@H](CC2CC2)N(CC#C)C3=NC(=C(S3)C)C4=C(C=C(C(=C4)C)OC)Cl)F

IUPAC name: 4-(2-chloro-4-methoxy-5-methylphenyl)-N-[(1S)-2-cyclopropyl-1-(3-fluoro-4-methylphenyl)ethyl]-5-methyl-N-prop-2-ynyl-1,3-thiazol-2-amine

Also known as: Crenessity, Crinecerfont, Nbi-74788, NBI-74788, Ssr 125543, Ssr-125543, Ssr125543, SSR125543, SSR-125543A, CRINECERFONT, CRINECERFONT HYDROCHLORIDE

Parent form; salt/anhydrous children: CHEMBL1628268

Patent coverage: 45 distinct patent families (140 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 98 (70%) 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
CRHR1	CRF1 receptor	Antagonist	8.7	0.4%	P34998

Broader ChEMBL bioactivity targets: 1 (assay-derived). Sample: Corticotropin-releasing factor receptor 1.

Bioactivity

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

Target	pChembl	Type	Value	Unit	Activity ID
CRHR1	6.62	Ki	240	nM	CHEMBL_ACT_118904

Target pathways

Aggregated over 1 target gene(s): CRHR1.

Top Reactome pathways

2 total, by targets touching each:

Pathway	Targets	Genes
Class B/2 (Secretin family receptors)	1	CRHR1
G alpha (s) signalling events	1	CRHR1

Dominant GO biological processes

GO term	Targets
immune response	1
cell surface receptor signaling pathway	1
adenylate cyclase-activating G protein-coupled receptor signaling pathway	1
activation of adenylate cyclase activity	1
female pregnancy	1
parturition	1
adrenal gland development	1
exploration behavior	1
fear response	1
behavioral response to ethanol	1
corticotropin secretion	1
general adaptation syndrome, behavioral process	1
cellular response to corticotropin-releasing hormone stimulus	1
negative regulation of voltage-gated calcium channel activity	1
regulation of corticosterone secretion	1

Indications & clinical

Indications

2 indications (1 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
congenital adrenal hyperplasia	4	MONDO:0018479	MONDO:0018479
depressive disorder	2	MONDO:0002050	MONDO:0002050

Clinical trials

Total trials: 7.

Phase distribution

Phase	Trials
PHASE2	5
PHASE3	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04490915	PHASE3	ACTIVE_NOT_RECRUITING	Global Safety and Efficacy Registration Study of Crinecerfont for Congenital Adrenal Hyperplasia
NCT04806451	PHASE3	ACTIVE_NOT_RECRUITING	Global Safety and Efficacy Registration Study of Crinecerfont in Pediatric Participants With Classic Congenital Adrenal Hyperplasia (CAHtalyst Pediatric Study)
NCT07187375	PHASE2	RECRUITING	Pharmacokinetics, Safety and Tolerability of Crinecerfont in Participants With Congenital Adrenal Hyperplasia Who Are Less Than 2 Years Old
NCT07536269	PHASE2	NOT_YET_RECRUITING	Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Crinecerfont in Participants With Classic Congenital Adrenal Hyperplasia (CAH) Who Are Less Than 4 Years Old
NCT01034995	PHASE2	COMPLETED	A Trial Evaluating the Efficacy and Tolerability of SSR125543 in Outpatients With Major Depressive Disorder
NCT03525886	PHASE2	COMPLETED	Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of NBI-74788 in Adults With Congenital Adrenal Hyperplasia
NCT04045145	PHASE2	COMPLETED	Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of NBI-74788 (Crinecerfont) in Pediatric Participants With Congenital Adrenal Hyperplasia

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.

17 molecules share ≥1 primary target. Top 17 by shared-target count:

Molecule	Source	Status	Shared targets
HYPERICIN	ChEMBL	Phase 3	CRHR1
PEXACERFONT	ChEMBL	Phase 3	CRHR1
EMICERFONT	ChEMBL	Phase 2	CRHR1
ONO-2333MS	ChEMBL	Phase 2	CRHR1
VERUCERFONT	ChEMBL	Phase 2	CRHR1
Aclidinium Bromide	PubChem	Approved	CRHR1
Alogliptin	PubChem	Approved	CRHR1
Belzutifan	PubChem	Approved	CRHR1
Bosentan	PubChem	Approved	CRHR1
Crizotinib	PubChem	Approved	CRHR1
Desloratadine	PubChem	Approved	CRHR1
Dihydroergotamine	PubChem	Approved	CRHR1
Fidaxomicin	PubChem	Approved	CRHR1
Methotrexate	PubChem	Approved	CRHR1
Propoxyphene	PubChem	Approved	CRHR1
Pyrazinamide	PubChem	Approved	CRHR1
Tiotropium Bromide Monohydrate	PubChem	Approved	CRHR1