Volinanserin

Summary

Volinanserin (CHEMBL74355) is a phase-3 clinical-stage small molecule targeting HTR2A, HTR2B, and HTR2C; indicated across 2 conditions including sleep disorder and depressive disorder.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 3 (HTR2A, HTR2B, HTR2C)
• Indications: 2 conditions
• Clinical trials: 5
• Chemistry: 373.5 Da · C22H28FNO3

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL74355
Name	Volinanserin
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	5311271
Molecular formula	C22H28FNO3
Molecular weight	373.5
InChIKey	HXTGXYRHXAGCFP-OAQYLSRUSA-N

SMILES: COC1=CC=CC(=C1OC)[C@@H](C2CCN(CC2)CCC3=CC=C(C=C3)F)O

IUPAC name: (R)-(2,3-dimethoxyphenyl)-[1-[2-(4-fluorophenyl)ethyl]piperidin-4-yl]methanol

Also known as: M-100907, M100907, MDL-100.907, Mdl-100907, MDL-100907, MDL100.907, Volinanserin, Volinanserina, Volinanserine, SID144210564, VOLINANSERIN, volinanserin

Parent form; salt/anhydrous children: CHEMBL5173614, CHEMBL5189294

Patent coverage: 232 distinct patent families (716 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 471 (66%) 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
HTR2A	5-HT2A receptor	Antagonist	9.3	0%	P28223
HTR2B	5-HT2B receptor	Antagonist	6	0.4%	P41595
HTR2C	5-HT2C receptor	Antagonist	7.7	0%	P28335

Broader ChEMBL bioactivity targets: 14 (assay-derived). Sample: 5-hydroxytryptamine receptor 2B, Potassium voltage-gated channel subfamily KQT member 1, Adrenergic receptor alpha-1, Alpha-2B adrenergic receptor, D(1A) dopamine receptor, D(2) dopamine receptor, 5-hydroxytryptamine receptor 2A, 5-hydroxytryptamine receptor 2C, Histamine H1 receptor, Alpha-1B adrenergic receptor.

Bioactivity

ChEMBL activities: 43 potent at pChembl ≥ 5 of 43 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
P14842	10	Ki	0.1	nM	CHEMBL_ACT_1422903
HTR2A	10	Ki	0.1	nM	CHEMBL_ACT_3561994
P14842	10	Ki	0.1	nM	CHEMBL_ACT_432180
HTR2A	9.85	Kd	0.14	nM	CHEMBL_ACT_24710269
HTR2A	9.52	Ki	0.3	nM	CHEMBL_ACT_610164
HTR2A	9.51	Ki	0.31	nM	CHEMBL_ACT_1422902
HTR2A	9.51	Ki	0.31	nM	CHEMBL_ACT_3304336
HTR2A	9.51	Ki	0.31	nM	CHEMBL_ACT_432179
P14842	9.44	Ki	0.36	nM	CHEMBL_ACT_2421191
HTR2A	9.44	Ki	0.36	nM	CHEMBL_ACT_956548
P14842	9.42	Ki	0.38	nM	CHEMBL_ACT_2419986
HTR2A	9.24	Ki	0.57	nM	CHEMBL_ACT_2099266
HTR2A	9.1	Ki	0.79	nM	CHEMBL_ACT_25740918
P14842	8.85	Ki	1.4	nM	CHEMBL_ACT_688688
HTR2A	8.82	Ki	1.5	nM	CHEMBL_ACT_688687
P14842	8.68	Ki	2.1	nM	CHEMBL_ACT_2099268
P14842	8.68	Ki	2.1	nM	CHEMBL_ACT_2419987
HTR2A	8.32	IC50	4.79	nM	CHEMBL_ACT_18579660
HTR2A	8.32	IC50	4.8	nM	CHEMBL_ACT_18579661
HTR2C	7.89	Ki	13	nM	CHEMBL_ACT_1422904
HTR2C	7.89	Ki	13	nM	CHEMBL_ACT_3304373
HTR2C	7.89	Ki	13	nM	CHEMBL_ACT_432181
OPRK1	6.99	Ki	102.7	nM	CHEMBL_ACT_25740920
HTR2C	6.97	Ki	107	nM	CHEMBL_ACT_2421192
HTR2C	6.94	Ki	113.9	nM	CHEMBL_ACT_25740919
HRH1	6.88	Ki	132.5	nM	CHEMBL_ACT_25740917
TMEM97	6.69	Ki	205	nM	CHEMBL_ACT_25740921
HTR2C	6.5	Ki	316.2	nM	CHEMBL_ACT_3561918
P15823	6.38	Ki	420	nM	CHEMBL_ACT_432183
DRD1	6.07	Ki	859.3	nM	CHEMBL_ACT_25740916

Target pathways

Aggregated over 3 target gene(s): HTR2A, HTR2B, HTR2C.

Top Reactome pathways

8 total, by targets touching each:

Pathway	Targets	Genes
Signal Transduction	3	HTR2A, HTR2B, HTR2C
Signaling by GPCR	3	HTR2A, HTR2B, HTR2C
Class A/1 (Rhodopsin-like receptors)	3	HTR2A, HTR2B, HTR2C
Amine ligand-binding receptors	3	HTR2A, HTR2B, HTR2C
GPCR downstream signalling	3	HTR2A, HTR2B, HTR2C
Serotonin receptors	3	HTR2A, HTR2B, HTR2C
G alpha (q) signalling events	3	HTR2A, HTR2B, HTR2C
GPCR ligand binding	3	HTR2A, HTR2B, HTR2C

Dominant GO biological processes

GO term	Targets
intracellular calcium ion homeostasis	3
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	3
phospholipase C-activating serotonin receptor signaling pathway	3
serotonin receptor signaling pathway	3
chemical synaptic transmission	3
positive regulation of phosphatidylinositol biosynthetic process	3
release of sequestered calcium ion into cytosol	3
positive regulation of ERK1 and ERK2 cascade	3
G protein-coupled serotonin receptor signaling pathway	3
signal transduction	3
G protein-coupled receptor signaling pathway	3
positive regulation of cell population proliferation	2
response to xenobiotic stimulus	2
positive regulation of fat cell differentiation	2
obsolete cGMP-mediated signaling	2

Indications & clinical

Indications

2 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
sleep disorder	3	MONDO:0100081	EFO:0008568
depressive disorder	2	MONDO:0002050	MONDO:0002050

Clinical trials

Total trials: 5.

Phase distribution

Phase	Trials
PHASE3	4
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00464061	PHASE3	TERMINATED	Efficacy an Safety of Volinanserin on Sleep Maintenance Insomnia With a Sub-study on Stable Type II Diabetes Mellitus
NCT00464243	PHASE3	COMPLETED	Efficacy and Safety of Volinanserin on Sleep Maintenance Insomnia - Polysomnographic Study
NCT00495885	PHASE3	COMPLETED	Efficacy and Safety of M100907 on Sleep Maintenance Insomnia With a Sub-study in Stable Type II Diabetes Mellitus
NCT00788515	PHASE3	TERMINATED	Comparison of Volinanserin and Lormetazepam in the Treatment of Insomnia Characterized by Sleep Maintenance Difficulties
NCT00070694	PHASE2	COMPLETED	An Investigation of the Antidepressant Efficacy of the 5-HT2A Antagonist, M100907, in Combination With Citalopram in Treatment Resistant Depression

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.

562 molecules share ≥1 primary target. Top 60 by shared-target count:

Molecule	Source	Status	Shared targets
DIHYDROERGOTAMINE	ChEMBL + PubChem	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
FIDAXOMICIN	ChEMBL + PubChem	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
PIMAVANSERIN	ChEMBL + PubChem	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
PROPOXYPHENE	ChEMBL + PubChem	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
ALOSETRON	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
AMIODARONE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
AMITRIPTYLINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
AMLODIPINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
AMOXAPINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
APOMORPHINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
ARIPIPRAZOLE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
ASENAPINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
ATOMOXETINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
AZATADINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
AZELASTINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
BENFLUOREX	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
BENPERIDOL	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
BENZQUINAMIDE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
BENZTROPINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
BREXPIPRAZOLE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
BROMOCRIPTINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
BUSPIRONE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
CANNABIDIOL	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
CARIPRAZINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
CARVEDILOL	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
CHLORHEXIDINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
CHLORPROMAZINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
CINACALCET	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
CISAPRIDE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
CITALOPRAM	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
CLEMASTINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
CLOMIPRAMINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
CLOTRIMAZOLE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
CLOZAPINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
CYCLIZINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
CYCLOBENZAPRINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
CYPROHEPTADINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
DAPIPRAZOLE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
DASATINIB	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
DESIPRAMINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
DESLORATADINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
DICYCLOMINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
DIETHYLSTILBESTROL	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
DIMENHYDRINATE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
DIPHENHYDRAMINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
DOMPERIDONE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
DOTHIEPIN	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
DOXAZOSIN	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
DOXEPIN	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
DROPERIDOL	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
DULOXETINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
EBASTINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
ECONAZOLE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
ENCAINIDE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
ERGOTAMINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
FLUOXETINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
FLUPHENAZINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
FLUSPIRILENE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
GUANABENZ	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C