Seltorexant

Summary

Seltorexant (CHEMBL3597971) is a phase-3 clinical-stage small molecule targeting HCRTR1 and HCRTR2; indicated across 7 conditions including major depressive disorder and insomnia.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 2 (HCRTR1, HCRTR2)
• Indications: 7 conditions
• Clinical trials: 31
• Chemistry: 407.4 Da · C21H22FN7O

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL3597971
Name	Seltorexant
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	67116280
Molecular formula	C21H22FN7O
Molecular weight	407.4
InChIKey	SQOCEMCKYDVLMM-UHFFFAOYSA-N

SMILES: CC1=CC(=NC(=N1)N2CC3CN(CC3C2)C(=O)C4=C(C=CC=C4F)N5N=CC=N5)C

IUPAC name: [2-(4,6-dimethylpyrimidin-2-yl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl]-[2-fluoro-6-(triazol-2-yl)phenyl]methanone

Also known as: JNJ-42847922, MIN-202, Seltorexant, US8653263, 107, SELTOREXANT

Parent form; salt/anhydrous children: CHEMBL4780973

Patent coverage: 48 distinct patent families (120 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 86 (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
HCRTR1	OX1 receptor	Antagonist	6.1	4.9%	O43613
HCRTR2	OX2 receptor	Antagonist	8.8		O43614

Broader ChEMBL bioactivity targets: 3 (assay-derived). Sample: Orexin receptor type 2, Orexin receptor type 2, Orexin/Hypocretin receptor type 1.

Bioactivity

ChEMBL activities: 19 potent at pChembl ≥ 5 of 19 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
HCRTR2	8.05	Ki	9	nM	CHEMBL_ACT_15654163
HCRTR2	8.05	Ki	9	nM	CHEMBL_ACT_16348877
HCRTR1	8.05	Ki	9	nM	CHEMBL_ACT_26977999
HCRTR2	8.05	Ki	9	nM	CHEMBL_ACT_28453226
HCRTR2	8.05	Ki	9	nM	CHEMBL_ACT_29017253
P56719	8	Ki	10	nM	CHEMBL_ACT_15622361
HCRTR2	8	Ki	10	nM	CHEMBL_ACT_15632789
HCRTR1	7.85	Ki	14	nM	CHEMBL_ACT_26979496
HCRTR2	7.85	Ki	14	nM	CHEMBL_ACT_28454723
HCRTR2	7.85	Ki	14	nM	CHEMBL_ACT_29018750
HCRTR1	6.1	Ki	800	nM	CHEMBL_ACT_15622312
HCRTR2	6.07	Ki	854	nM	CHEMBL_ACT_26979499
HCRTR1	6.07	Ki	854	nM	CHEMBL_ACT_28454726
HCRTR1	6.07	Ki	854	nM	CHEMBL_ACT_29018753
HCRTR1	6.06	Ki	868	nM	CHEMBL_ACT_16300573
HCRTR2	6.06	Ki	868	nM	CHEMBL_ACT_26978002
HCRTR1	6.06	Ki	868	nM	CHEMBL_ACT_28453229
HCRTR1	6.06	Ki	868	nM	CHEMBL_ACT_29017256
HCRTR1	5.89	Ki	1277	nM	CHEMBL_ACT_15654162

Target pathways

Aggregated over 2 target gene(s): HCRTR1, HCRTR2.

Top Reactome pathways

2 total, by targets touching each:

Pathway	Targets	Genes
Orexin and neuropeptides FF and QRFP bind to their respective receptors	2	HCRTR1, HCRTR2
G alpha (q) signalling events	2	HCRTR1, HCRTR2

Dominant GO biological processes

GO term	Targets
neuropeptide signaling pathway	2
chemical synaptic transmission	2
feeding behavior	2
cellular response to hormone stimulus	2
regulation of cytosolic calcium ion concentration	2
signal transduction	2
G protein-coupled receptor signaling pathway	2
positive regulation of ERK1 and ERK2 cascade	1
phospholipase C-activating G protein-coupled receptor signaling pathway	1
regulation of circadian sleep/wake cycle, wakefulness	1
circadian sleep/wake cycle process	1
locomotion	1
glucose homeostasis	1

Indications & clinical

Indications

7 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
insomnia	2	MONDO:0013600	EFO:0004698
Alzheimer disease	2	MONDO:0004975	MONDO:0004975
obstructive sleep apnea syndrome	1	MONDO:0007147	EFO:0003918
kidney disorder	1	MONDO:0005240	EFO:0003086
liver disorder	1	MONDO:0005154	EFO:0001421

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

Clinical trials

Total trials: 31.

Phase distribution

Phase	Trials
PHASE1	21
PHASE3	5
PHASE2	5

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06559306	PHASE3	RECRUITING	Phase 3 Study of Adjunctive Treatment With Seltorexant in Adult and Elderly Participants With Major Depressive Disorder and Insomnia Symptoms
NCT07573176	PHASE3	RECRUITING	A Study of Seltorexant as Monotherapy in Adults and Elderly Participants With Major Depressive Disorder
NCT04513912	PHASE3	COMPLETED	A Study of Seltorexant Compared to Quetiapine XR as Adjunctive Therapy to Antidepressants in Adult and Elderly Participants With Major Depressive Disorder With Insomnia Symptoms Who Have Responded Inadequately to Antidepressant Therapy
NCT04532749	PHASE3	TERMINATED	A Study of Seltorexant as Adjunctive Therapy to Antidepressants in Adult and Elderly Participants With Major Depressive Disorder With Insomnia Symptoms Who Have Responded Inadequately to Antidepressant Therapy
NCT04533529	PHASE3	COMPLETED	A Study of Seltorexant as Adjunctive Therapy to Antidepressants in Adult and Elderly Participants With Major Depressive Disorder With Insomnia Symptoms Who Have Responded Inadequately to Antidepressant and Long-term Safety Extension Treatment With Seltorexant
NCT02464046	PHASE2	COMPLETED	Study to Evaluate Efficacy, Safety and Tolerability of JNJ-42847922 in Participants With Insomnia Disorder Without Psychiatric Comorbidity
NCT03227224	PHASE2	COMPLETED	A Study to Evaluate the Efficacy and Safety of JNJ-42847922 as Adjunctive Therapy to Antidepressants in Adult Participants With Major Depressive Disorder Who Have Responded Inadequately to Antidepressant Therapy
NCT03321526	PHASE2	COMPLETED	A Study to Compare the Efficacy, Safety, and Tolerability of JNJ-42847922 Versus Quetiapine Extended-Release as Adjunctive Therapy to Antidepressants in Adult Participants With Major Depressive Disorder Who Have Responded Inadequately to Antidepressant Therapy
NCT03375203	PHASE2	COMPLETED	A Study to Evaluate the Efficacy, Safety, and Tolerability of JNJ-42847922 in Participants With Insomnia Disorder
NCT05307692	PHASE2	COMPLETED	A Study of Seltorexant in Participants With Probable Alzheimer’s Disease
NCT02067299	PHASE1	COMPLETED	A Study to Investigate the Effect of JNJ-42847922 on Polysomnography Measures in Patients With Major Depressive Disorder With Insomnia Who Are Stably Treated With Antidepressants
NCT02230878	PHASE1	COMPLETED	A Study to Investigate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of JNJ-42847922 in Healthy Participants
NCT02455856	PHASE1	COMPLETED	Study to Investigate Effects of Repeated Administration of Itraconazole on Pharmacokinetics of JNJ-42847922 in Healthy Male Participants
NCT02475161	PHASE1	COMPLETED	A Study to Investigate the Effect of Increased Gastric pH on the Oral Bioavailability of the Orexin-2 Receptor Antagonist JNJ-42847922 in Healthy Participants
NCT02476058	PHASE1	COMPLETED	A Safety, Efficacy and Biomarker Study of JNJ-42847922 in Participants With Major Depressive Disorder
NCT02555124	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability and Pharmacokinetics of JNJ-42847922 in Healthy Japanese Male Participants
NCT02578472	PHASE1	COMPLETED	Pilot Study to Evaluate the Duration of Effects on Simulated Car Driving and Cognitive Performance After a Single Dose of JNJ-42847922, Zolpidem and Placebo in Healthy Participants
NCT02617810	PHASE1	COMPLETED	A Study to Assess the Effect of Multiple-Dose Administration of JNJ-42847922 on Midazolam and Warfarin in Healthy Participants
NCT02661893	PHASE1	COMPLETED	A Drug Interaction Study in Healthy Participants to Assess the Effect of Rifampin on the Pharmacokinetics of JNJ-42847922
NCT02837692	PHASE1	COMPLETED	A Study to Assess the Effects of Age and Gender on the Pharmacokinetics of JNJ-42847922 in Healthy Adults
NCT03249402	PHASE1	COMPLETED	A Study to Evaluate the Effect of Multiple Oral Doses of JNJ-42847922 on the Steady-state Pharmacokinetics of an Oral Contraceptive Containing Ethinyl Estradiol and Levonorgestrel in Healthy Female Adult Participants
NCT03374475	PHASE1	COMPLETED	A Study to Investigate the Antidepressant Mechanism-of-action of JNJ-42847922 in Participants With Major Depressive Disorder
NCT03438461	PHASE1	COMPLETED	A Study to Evaluate the Relative Oral Bioavailability of Seltorexant (JNJ-42847922) After Administration of 3 Different Formulations in Healthy Participants Under Fasted and Semi-fasted Conditions
NCT03494907	PHASE1	COMPLETED	A Study to Evaluate the Effects of Single-dose Seltorexant on Electrocardiogram Intervals in Healthy Adult Participants
NCT03796026	PHASE1	COMPLETED	A Study to Assess the Effect of Seltorexant Compared to Placebo on Respiration During Sleep in Adult Participants With Obstructive Sleep Apnea
NCT04553042	PHASE1	COMPLETED	A Study of Seltorexant in Healthy Participants
NCT04616677	PHASE1	COMPLETED	A Study to Evaluate the Effect of Renal Impairment on JNJ-42847922 in Adult Participants
NCT04951609	PHASE1	TERMINATED	A Study of Seltorexant as Adjunctive Therapy to Antidepressants in Adolescents With Major Depressive Disorder Who Have an Inadequate Response to Selective Serotonin Reuptake Inhibitor (SSRI) and Psychotherapy
NCT04960124	PHASE1	COMPLETED	A Study to Evaluate the Effect of Hepatic Impairment on JNJ-42847922 in Adult Participants
NCT05106153	PHASE1	COMPLETED	A Study to Determine the Abuse Potential of Seltorexant Compared to Suvorexant and Zolpidem
NCT05236868	PHASE1	COMPLETED	A Study of JNJ-42847922 (Seltorexant) in Healthy 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.

10 molecules share ≥1 primary target. Top 10 by shared-target count:

Molecule	Source	Status	Shared targets
DARIDOREXANT	ChEMBL	Phase 4 (approved)	HCRTR1, HCRTR2
LEMBOREXANT	ChEMBL	Phase 4 (approved)	HCRTR1, HCRTR2
SUVOREXANT	ChEMBL	Phase 4 (approved)	HCRTR1, HCRTR2
ALMOREXANT	ChEMBL	Phase 3	HCRTR1, HCRTR2
FILOREXANT	ChEMBL	Phase 2	HCRTR1, HCRTR2
NIVASOREXANT	ChEMBL	Phase 2	HCRTR1, HCRTR2
SB-649868	ChEMBL	Phase 2	HCRTR1, HCRTR2
NALFURAFINE	ChEMBL	Phase 4 (approved)	HCRTR1
DANAVOREXTON	ChEMBL	Phase 2	HCRTR2
Belzutifan	PubChem	Approved	HCRTR1