Suvorexant

Summary

Suvorexant (CHEMBL1083659) is an approved small-molecule central nervous system depressant (ATC N05CJ01) targeting HCRTR1 and HCRTR2; indicated across 11 conditions including insomnia and delirium.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: N05CJ01
• Targets: 2 (HCRTR1, HCRTR2)
• Indications: 11 conditions
• Clinical trials: 62
• Chemistry: 450.9 Da · C23H23ClN6O2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL1083659
Name	Suvorexant
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	24965990
ChEBI	CHEBI:82698
ATC	N05CJ01
Molecular formula	C23H23ClN6O2
Molecular weight	450.9
InChIKey	JYTNQNCOQXFQPK-MRXNPFEDSA-N

SMILES: C[C@@H]1CCN(CCN1C(=O)C2=C(C=CC(=C2)C)N3N=CC=N3)C4=NC5=C(O4)C=CC(=C5)Cl

IUPAC name: [(7R)-4-(5-chloro-1,3-benzoxazol-2-yl)-7-methyl-1,4-diazepan-1-yl]-[5-methyl-2-(triazol-2-yl)phenyl]methanone

ChEBI definition: An aromatic amide obtained by formal condensation of the carboxy group of 5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoic acid with the secondary amino group of 5-chloro-2-[(5R)-5-methyl-1,4-diazepan-1-yl]-1,3-benzoxazole. An orexin receptor antagonist used for the management of insomnia.

Pharmacological roles (ChEBI): central nervous system depressant, orexin receptor antagonist.

Also known as: Belsomra, MK-4305, MK4305, Suvorexant, Suvorexant component of belsomra, SUVOREXANT, suvorexant

Patent coverage: 397 distinct patent families (852 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 689 (81%) 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	8.7	4.9%	O43613
HCRTR2	OX2 receptor	Antagonist	9.4		O43614

Broader ChEMBL bioactivity targets: 7 (assay-derived). Sample: Alpha-2B adrenergic receptor, Voltage-gated inwardly rectifying potassium channel KCNH2, Orexin receptor type 2, Orexin/Hypocretin receptor type 1, Nuclear receptor subfamily 1 group I member 2, Orexin receptor type 2, Orexin/Hypocretin receptor type 1.

Bioactivity

ChEMBL activities: 28 potent at pChembl ≥ 5 of 30 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
HCRTR2	9.46	Ki	0.35	nM	CHEMBL_ACT_3313252
HCRTR2	9.4	Ki	0.4	nM	CHEMBL_ACT_13399794
HCRTR2	9.4	Ki	0.4	nM	CHEMBL_ACT_14656689
HCRTR2	9.4	IC50	0.4	nM	CHEMBL_ACT_15739951
HCRTR1	9.4	Ki	0.4	nM	CHEMBL_ACT_19153604
HCRTR1	9.26	Ki	0.55	nM	CHEMBL_ACT_3313249
HCRTR1	9.26	Ki	0.55	nM	CHEMBL_ACT_3313250
HCRTR1	9.22	Ki	0.6	nM	CHEMBL_ACT_13399795
HCRTR1	9.22	Ki	0.6	nM	CHEMBL_ACT_14656673
HCRTR1	9.17	Ki	0.68	nM	CHEMBL_ACT_26164714
HCRTR1	9.17	IC50	0.68	nM	CHEMBL_ACT_29214141
HCRTR2	9.1	Ki	0.79	nM	CHEMBL_ACT_19153615
HCRTR2	8.89	IC50	1.3	nM	CHEMBL_ACT_29214144
P58307	8.77	Ki	1.7	nM	CHEMBL_ACT_13478572
HCRTR1	8.51	Ki	3.09	nM	CHEMBL_ACT_22895920
P58308	8.06	Ki	8.71	nM	CHEMBL_ACT_13478570
HCRTR2	7.93	Ki	11.8	nM	CHEMBL_ACT_15129761
HCRTR1	7.3	IC50	50	nM	CHEMBL_ACT_14656705
HCRTR1	7.3	IC50	50	nM	CHEMBL_ACT_16492919
HCRTR1	7.3	IC50	50	nM	CHEMBL_ACT_3313251
HCRTR2	7.25	IC50	56	nM	CHEMBL_ACT_14656721
HCRTR2	7.25	IC50	56	nM	CHEMBL_ACT_16492912
HCRTR2	7.25	IC50	56	nM	CHEMBL_ACT_3313253
HCRTR2	6.86	IC50	138	nM	CHEMBL_ACT_17988759
HCRTR2	6.86	IC50	138	nM	CHEMBL_ACT_26123583
HCRTR1	6.7	IC50	199	nM	CHEMBL_ACT_17988730
HCRTR1	6.7	IC50	199	nM	CHEMBL_ACT_26123581
NR1I2	5.36	AC50	4400	nM	CHEMBL_ACT_25188497

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

11 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
insomnia	4	MONDO:0013600	EFO:0004698
delirium	3	MONDO:0045057	EFO:0009267
restless legs syndrome	2	MONDO:0005391	EFO:0004270
sleep disorder	2	MONDO:0100081	EFO:0008568
opiate dependence	2	MONDO:0005530	EFO:0010702
Alzheimer disease	2	MONDO:0004975	MONDO:0004975
alcohol abuse	2	MONDO:0002046	MONDO:0007079
autism	2	MONDO:0005260	EFO:0003758
sleep apnea syndrome	1	MONDO:0005296	EFO:0003877
nicotine dependence	1	MONDO:0008575	EFO:0003768

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

Clinical trials

Total trials: 62.

Phase distribution

Phase	Trials
PHASE4	25
PHASE2	15
PHASE1	9
EARLY_PHASE1	5
PHASE3	4
Not specified	2
PHASE2/PHASE3	1
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03642028	PHASE4	RECRUITING	Suvorexant: A Dual Orexin Receptor Antagonist for Treating Sleep Disturbance in Posttraumatic Stress
NCT05823844	PHASE4	RECRUITING	Efficacy of Suvorexant on Post-operative Sleep Disturbance
NCT06584942	PHASE4	RECRUITING	Evaluation of Suvorexant for Reduction of Brain Reactivity in Patients With Cannabis Use Disorder (Pilot Study)
NCT06788522	PHASE4	NOT_YET_RECRUITING	The Effects of Orexin Antagonism on Fear Extinction in PTSD
NCT02491788	PHASE4	COMPLETED	Examination of the Effectiveness of Suvorexant in Improving Daytime Sleep in Shift Workers
NCT02527564	PHASE4	COMPLETED	Efficacy of Suvorexant to Treat Insomnia Related to Bipolar Disorder
NCT02593682	PHASE4	COMPLETED	The Role of Orexin in Human Panic Disorder
NCT02669030	PHASE4	UNKNOWN	A Six Week, Randomized, Double-Blind Placebo-Controlled, Suvorexant Augmentation Study of Antidepressant Treatment of Major Depressive Disorder With Residual Insomnia
NCT02684136	PHASE4	TERMINATED	Suvorexant in Insomnia Co-morbid With Fibromyalgia
NCT02704754	PHASE4	COMPLETED	Suvorexant and Trauma Related Insomnia
NCT02729714	PHASE4	COMPLETED	A Pilot Study of Suvorexant for Insomnia in Parkinson Disease
NCT02849184	PHASE4	COMPLETED	To Compare the Effectiveness of Suvorexant vs Placebo on Sleep Pressure in Hypertensives With Insomnia
NCT02849548	PHASE4	COMPLETED	Suvorexant and Sleep’s Benefits to Therapeutic Exposure for Posttraumatic Stress Disorder
NCT03034018	PHASE4	COMPLETED	Efficacy of Suvorexant in the Treatment of Hot Flash-associated Insomnia
NCT03110315	PHASE4	COMPLETED	A Study of Suvorexant in Patients With Multiple Sclerosis Fatigue and Insomnia
NCT03312517	PHASE4	COMPLETED	Study to Compare the Awakening Threshold Effects of Belsomra 10 mg and 20 mg to Placebo in Non-elderly Insomniacs
NCT03764683	PHASE4	WITHDRAWN	Suvorexant (Belsomra) for the Treatment of Bipolar Depression With Insomnia
NCT03768713	PHASE4	UNKNOWN	Impact of Suvorexant on Sympathetic Nerve Activity and Baroreflex Function in Chronic Insomnia
NCT03818581	PHASE4	COMPLETED	Suvorexant on Sleep Disturbance in Patients With Chronic Insomnia and Suboptimally Controlled Type 2 Diabetes
NCT04014387	PHASE4	COMPLETED	Treatment of Disturbed Sleep in Progressive Supranuclear Palsy (PSP)
NCT04092894	PHASE4	COMPLETED	Suvorexant and Sleep/Delirium in ICU Patients
NCT04706091	PHASE4	COMPLETED	Efficacy of Suvorexant in Patients With Effectively Treated Restless Legs Syndrome and Persistent Chronic Insomnia
NCT05593653	PHASE4	COMPLETED	Treating Insomnia and Improving Metabolic Health in Midlife Women With Insomnia
NCT06162663	PHASE4	TERMINATED	Double-blind Randomized Controlled Trial Comparing Suvorexant 20 mg to Placebo for Treatment of Insomnia in Cancer Survivors
NCT06834386	PHASE4	WITHDRAWN	Suvorexant for Insomnia to Prevent Delirium in Hospitalized Cancer Patients
NCT06655883	PHASE3	RECRUITING	A Study of Suvorexant (MK-4305) for the Treatment of Insomnia Disorder in Participants With Opioid Use Disorder (MK-4305-098)
NCT01021813	PHASE3	COMPLETED	A Long Term Safety Study of Suvorexant in Participants With Primary Insomnia (MK-4305-009 AM3)
NCT02750306	PHASE3	COMPLETED	Safety and Efficacy of Suvorexant (MK-4305) for the Treatment of Insomnia in Participants With Alzheimer’s Disease (MK-4305-061)
NCT03412591	PHASE2/PHASE3	COMPLETED	The Efficacy of Suvorexant in Treatment of Patients With Substance Use Disorder and Insomnia: A Pilot Open Trial
NCT04571944	PHASE3	COMPLETED	Efficacy and Safety of Suvorexant (MK-4305) for Reducing Incidence of Delirium in Japanese Participants at High Risk of Delirium (MK-4305-085)
NCT04629547	PHASE2	RECRUITING	Sleep Trial to Prevent Alzheimer’s Disease
NCT05145764	PHASE2	RECRUITING	Suvorexant as an Adjunct to Buprenorphine in Persons Who Use Fentanyl
NCT05546554	PHASE2	RECRUITING	Trial of Suvorexant for Sleep in Children With Autism
NCT06484075	PHASE1/PHASE2	RECRUITING	Suvorexant for Alcohol Use Disorder (AUD): Neural Mechanisms
NCT06679062	PHASE2	RECRUITING	Suvorexant for Treatment of AUD and PTSD
NCT07214207	PHASE2	RECRUITING	Orexin Receptor Antagonism for the Treatment of Alcohol Use Disorder and Stress-Related Drinking
NCT00792298	PHASE2	COMPLETED	Phase IIB 2-Period Crossover Polysomnography Study in Participants With Primary Insomnia (MK-4305-006)
NCT02785406	PHASE2	COMPLETED	Role of the Orexin Receptor System in Stress, Sleep and Cocaine Use
NCT03755310	PHASE2	UNKNOWN	Treatment of Restless Legs Syndrome With the Hypocretin Antagonist Suvorexant
NCT03897062	PHASE2	TERMINATED	Suvorexant in the Management Comorbid Sleep Disorder and Alcohol Dependence

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
ALMOREXANT	ChEMBL	Phase 3	HCRTR1, HCRTR2
SELTOREXANT	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