Lemborexant

Summary

Lemborexant (CHEMBL3545367) is an approved small molecule (ATC N05CJ02) targeting HCRTR1 and HCRTR2; indicated across 9 conditions including insomnia and sleep disorder.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: N05CJ02
• Targets: 2 (HCRTR1, HCRTR2)
• Indications: 9 conditions
• Clinical trials: 47
• Chemistry: 410.4 Da · C22H20F2N4O2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL3545367
Name	Lemborexant
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	56944144
ATC	N05CJ02
Molecular formula	C22H20F2N4O2
Molecular weight	410.4
InChIKey	MUGXRYIUWFITCP-PGRDOPGGSA-N

SMILES: CC1=NC(=NC=C1OC[C@]2(C[C@H]2C(=O)NC3=NC=C(C=C3)F)C4=CC(=CC=C4)F)C

IUPAC name: cis-(1R,2S)-2-[(2,4-dimethylpyrimidin-5-yl)oxymethyl]-2-(3-fluorophenyl)-N-(5-fluoro-2-pyridinyl)cyclopropane-1-carboxamide

Also known as: Dayvigo, E-2006, E2006, Lemborexant, LEMBOREXANT

Patent coverage: 120 distinct patent families (271 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 242 (89%) 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	8.6	4.9%	O43613
HCRTR2	OX2 receptor	Antagonist	9.3		O43614

Broader ChEMBL bioactivity targets: 3 (assay-derived). Sample: Voltage-gated inwardly rectifying potassium channel KCNH2, Orexin receptor type 2, Orexin/Hypocretin receptor type 1.

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
HCRTR2	9.36	Ki	0.44	nM	CHEMBL_ACT_15623331
HCRTR2	9.3	Ki	0.5	nM	CHEMBL_ACT_19153617
HCRTR1	8.6	Ki	2.51	nM	CHEMBL_ACT_19153603
HCRTR2	8.52	Ki	3	nM	CHEMBL_ACT_15623213
HCRTR1	8.24	Ki	5.7	nM	CHEMBL_ACT_15623332
HCRTR1	8.22	Ki	6	nM	CHEMBL_ACT_15623241
KCNH2	5.21	IC50	6100	nM	CHEMBL_ACT_15623314

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

9 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
sleep disorder	3	MONDO:0100081	EFO:0008568
alcohol abuse	3	MONDO:0002046	MONDO:0007079
epilepsy	3	MONDO:0005027	EFO:0000474
circadian rhythm sleep disorder	2	MONDO:0024361	MONDO:0024361
Alzheimer disease	2	MONDO:0004975	MONDO:0004975
liver disorder	1	MONDO:0005154	EFO:0001421
obstructive sleep apnea syndrome	1	MONDO:0007147	EFO:0003918
kidney disorder	1	MONDO:0005240	EFO:0003086

Clinical trials

Total trials: 47.

Phase distribution

Phase	Trials
PHASE1	18
PHASE2	11
PHASE4	6
PHASE3	6
Not specified	5
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06093126	PHASE4	RECRUITING	Lemborexant for Insomnia in a Patient With Dementia: An N-of-1 Trial
NCT06874855	PHASE4	RECRUITING	Lemborexant in Delayed Sleep Phase Syndrome
NCT07384429	PHASE4	RECRUITING	Effects of Lemborexant on Motor-sleep Comorbidity in Parkinson’s Disease
NCT07407400	PHASE4	NOT_YET_RECRUITING	Lemborexant for Sleep and Delirium Prevention in Elderly ICU Patients
NCT05344443	PHASE4	COMPLETED	Lemborexant Shift Work Treatment Study
NCT05463861	PHASE4	COMPLETED	Lemborexant in Delayed Sleep Phase Syndrome
NCT06262594	PHASE3	RECRUITING	Lemborexant Treatment of Insomnia Linked to Epilepsy
NCT06496282	PHASE3	RECRUITING	Lemborexant on Improving Sleep Quality Among Hospital Rotating Shift Workers
NCT02783729	PHASE3	COMPLETED	Study of the Efficacy and Safety of Lemborexant in Subjects 55 Years and Older With Insomnia Disorder (SUNRISE 1)
NCT02952820	PHASE3	COMPLETED	Long-term Study of Lemborexant in Insomnia Disorder (SUNRISE 2)
NCT04549168	PHASE3	COMPLETED	A Study of Lemborexant in Chinese Participants With Insomnia Disorder
NCT05458609	PHASE3	COMPLETED	Lemborexant Augmentation of Naltrexone for Alcohol Craving and Sleep
NCT06274528	PHASE2	RECRUITING	DORA and LP in Alzheimer’s Disease Biomarkers
NCT06648681	PHASE2	NOT_YET_RECRUITING	Lemborexant to Prevent Post-operative Delirium in Cardiac Surgery Patients
NCT06823752	PHASE2	RECRUITING	A Dual Orexin Receptor Antagonist to Reduce Biomarkers of Neurodegeneration in Adults With Insomnia.
NCT06843187	PHASE2	RECRUITING	Lemborexant for the Treatment of Residual Insomnia in Major Depressive Disorder (MDD)
NCT06928766	PHASE2	NOT_YET_RECRUITING	Effects of Eszopiclone and Lemborexant in People With OSA With a Low Arousal Threshold Who Have Difficulty Sleeping
NCT06981195	PHASE2	RECRUITING	Effects of Lemborexant on Insomnia and Its Relationship to Mood and Behavior on Opioid Use Disorder Subjects
NCT01995838	PHASE2	COMPLETED	A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Bayesian Adaptive Randomization Design, Dose Response Study of the Efficacy of E2006 in Adults and Elderly Subjects With Chronic Insomnia
NCT03001557	PHASE2	COMPLETED	Study of Lemborexant for Irregular Sleep-Wake Rhythm Disorder and Mild to Moderate Alzheimer’s Disease Dementia
NCT04818086	PHASE1/PHASE2	COMPLETED	Drug-drug Interaction Study of Lemborexant as an Adjunctive Treatment for Buprenorphine/Naloxone for Opioid Use Disorder
NCT05594589	PHASE2	COMPLETED	A Study to Assess the Pharmacodynamics of Lemborexant in Korean Participants With Insomnia Disorder
NCT05728736	PHASE2	WITHDRAWN	Acute Effect of Lemborexant on CSF Amyloid-Beta and Tau
NCT07480096	PHASE2	COMPLETED	Efficacy and Safety of Lemborexant for Patients With Cirrhosis and Sleep Problems
NCT01463098	PHASE1	COMPLETED	A 2-Part Single Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of E2006
NCT01673451	PHASE1	COMPLETED	2-Part Multiple Ascending Dose Study for Safety and Pharmacokinetics in Healthy and Elderly Subjects
NCT01673880	PHASE1	COMPLETED	Open-Label Study of Bioavailability of E2006 Tablet Versus Capsule Formulations
NCT02039089	PHASE1	COMPLETED	A Two-Part Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of E2006 in Healthy Japanese and White Subjects
NCT02046213	PHASE1	COMPLETED	An Open-label, Single-dose Study to Determine the Metabolism and Excretion of [14C]E2006 in Healthy Male Subjects
NCT02085967	PHASE1	COMPLETED	A 2-Part Study to Assess Potential Metabolism-Based Drug-Drug Interactions of E2006 When Coadministered With Itraconazole, Rifampin, Midazolam, or Bupropion
NCT02089412	PHASE1	COMPLETED	A Study to Determine the Effect of a High-Fat Meal on the Rate and Extent of E2006 Absorption in Healthy Subjects
NCT02350309	PHASE1	COMPLETED	Study to Evaluate the Effect of 2 Dosage Strengths of Lemborexant (E2006) on a Multiple Sleep Latency Test in Participants With Insomnia Disorder
NCT02583451	PHASE1	COMPLETED	Study to Evaluate the Effect of Lemborexant Versus Placebo on Driving Performance in Healthy Adult and Elderly Subjects
NCT03158025	PHASE1	COMPLETED	A Study to Determine the Abuse Potential of Single Oral Doses of Lemborexant Compared to Zolpidem, Suvorexant and Placebo in Healthy, Non-Dependent, Recreational Sedative Users
NCT03440424	PHASE1	COMPLETED	Study to Evaluate the Pharmacokinetics of Lemborexant (E2006) and Its Metabolites in Subjects With Mild and Moderate Hepatic Impairment Compared to Healthy Subjects
NCT03443063	PHASE1	COMPLETED	Study to Evaluate the Pharmacokinetics of Lemborexant (E2006) and Its Metabolites in Subjects With Normal Renal Function or With Severe Renal Impairment
NCT03451110	PHASE1	COMPLETED	Study to Assess the Pharmacokinetic Drug-Drug Interactions of Lemborexant When Coadministered With an Oral Contraceptive, Famotidine, or Fluconazole in Healthy Subjects
NCT03471871	PHASE1	COMPLETED	Study to Evaluate the Respiratory Safety of Lemborexant in Adult and Elderly Healthy Subjects and Adult and Elderly Subjects With Mild Obstructive Sleep Apnea
NCT03483636	PHASE1	COMPLETED	Study of Lemborexant-Alcohol Interaction in Healthy Subjects
NCT04555733	PHASE1	COMPLETED	A Single and Multiple Dose Study of Lemborexant in Healthy Chinese Participants

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

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
SUVOREXANT	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