Almorexant

Summary

Almorexant (CHEMBL455136) is a phase-3 clinical-stage small molecule targeting HCRTR1 and HCRTR2; indicated across 1 condition including insomnia.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 2 (HCRTR1, HCRTR2)
• Indications: 1 condition
• Clinical trials: 6
• Chemistry: 512.6 Da · C29H31F3N2O3

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL455136
Name	Almorexant
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	23727689
Molecular formula	C29H31F3N2O3
Molecular weight	512.6
InChIKey	DKMACHNQISHMDN-RPLLCQBOSA-N

SMILES: CNC(=O)[C@@H](C1=CC=CC=C1)N2CCC3=CC(=C(C=C3[C@@H]2CCC4=CC=C(C=C4)C(F)(F)F)OC)OC

IUPAC name: (2R)-2-[(1S)-6,7-dimethoxy-1-[2-[4-(trifluoromethyl)phenyl]ethyl]-3,4-dihydro-1H-isoquinolin-2-yl]-N-methyl-2-phenylacetamide

Also known as: ACT-078573, Almorexant, almorexant, ALMOREXANT, ALMOREXANT (HYDROCHLORIDE), Almorexant (hydrochloride)

Parent form; salt/anhydrous children: CHEMBL3542330

Patent coverage: 88 distinct patent families (218 SureChEMBL compound mentions), from 2 matched compound structure(s). 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	7.8	4.9%	O43613
HCRTR2	OX2 receptor	Antagonist	8.9		O43614

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

Bioactivity

ChEMBL activities: 13 potent at pChembl ≥ 5 of 13 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
HCRTR1	8.57	Ki	2.67	nM	CHEMBL_ACT_29213930
HCRTR2	8.52	Ki	3	nM	CHEMBL_ACT_29213941
HCRTR2	8.33	Ki	4.7	nM	CHEMBL_ACT_15129759
HCRTR2	8.1	IC50	8	nM	CHEMBL_ACT_13360578
HCRTR2	8.1	Ki	8	nM	CHEMBL_ACT_13399796
HCRTR2	8.1	IC50	8	nM	CHEMBL_ACT_16492922
HCRTR2	8.1	IC50	8	nM	CHEMBL_ACT_2386386
HCRTR1	7.89	IC50	13	nM	CHEMBL_ACT_13360601
HCRTR1	7.89	Ki	13	nM	CHEMBL_ACT_13399797
HCRTR1	7.89	IC50	13	nM	CHEMBL_ACT_16492921
HCRTR1	7.89	IC50	13	nM	CHEMBL_ACT_2386350
HCRTR1	6.92	IC50	119	nM	CHEMBL_ACT_13421820
HCRTR2	5.09	IC50	8100	nM	CHEMBL_ACT_13421817

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

1 indication (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
insomnia	3	MONDO:0013600	EFO:0004698

Clinical trials

Total trials: 6.

Phase distribution

Phase	Trials
PHASE1	3
PHASE3	1
PHASE2	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00608985	PHASE3	COMPLETED	Almorexant (ACT 078573) in Adult Subjects With Chronic Primary Insomnia
NCT00606593	PHASE2	COMPLETED	Almorexant (ACT-078573) in Elderly Subjects With Chronic Primary Insomnia
NCT00640848	PHASE1	COMPLETED	Almorexant in Primary Insomnia
NCT01954589	PHASE1	COMPLETED	Single-ascending Dose Study to Investigate the Tolerability, Safety, Pharmacokinetics, and Pharmacodynamics of ACT-462206
NCT01987739	PHASE1	COMPLETED	Study to Evaluate the Relative Abuse Potential of Almorexant in Recreational Drug Users
NCT01243060	Not specified	COMPLETED	Effect of a Hypocretin/Orexin Antagonist on Neurocognitive Performance

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
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