Soticlestat

Summary

Soticlestat (CHEMBL4298172) is a phase-3 clinical-stage small molecule targeting CYP46A1; indicated across 5 conditions including lennox-gastaut syndrome and complex regional pain syndrome.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 1 (CYP46A1)
• Indications: 5 conditions
• Clinical trials: 21
• Chemistry: 373.4 Da · C23H23N3O2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL4298172
Name	Soticlestat
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	73437845
Molecular formula	C23H23N3O2
Molecular weight	373.4
InChIKey	XKUZMIUSBMCVPP-UHFFFAOYSA-N

SMILES: C1CN(CCC1(CC2=CC=CC=C2)O)C(=O)C3=C(N=CC=C3)C4=CC=NC=C4

IUPAC name: (4-benzyl-4-hydroxypiperidin-1-yl)-(2-pyridin-4-yl-3-pyridinyl)methanone

Also known as: OV-935, OV935, Soticlestat, TAK-935, TAK935, SOTICLESTAT

Patent coverage: 27 distinct patent families (88 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
CYP46A1	CYP46A1	Inhibition	8.35	0.2%	Q9Y6A2

Broader ChEMBL bioactivity targets: 5 (assay-derived). Sample: Cytochrome P450 2C9, Cytochrome P450 3A4, Cytochrome P450 2C19, Cytochrome P450 2C8, Cholesterol 24-hydroxylase.

Bioactivity

ChEMBL activities: 3 potent at pChembl ≥ 5 of 6 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
CYP46A1	8.13	IC50	7.4	nM	CHEMBL_ACT_24395288
CYP46A1	8.13	IC50	7.4	nM	CHEMBL_ACT_25012757
CYP3A4	5.18	IC50	6600	nM	CHEMBL_ACT_25012792

Target pathways

Aggregated over 1 target gene(s): CYP46A1.

Top Reactome pathways

2 total, by targets touching each:

Pathway	Targets	Genes
Synthesis of bile acids and bile salts via 24-hydroxycholesterol	1	CYP46A1
Endogenous sterols	1	CYP46A1

Dominant GO biological processes

GO term	Targets
bile acid biosynthetic process	1
cholesterol catabolic process	1
xenobiotic metabolic process	1
nervous system development	1
sterol metabolic process	1
progesterone metabolic process	1
regulation of long-term synaptic potentiation	1
protein localization to membrane raft	1
lipid metabolic process	1
steroid metabolic process	1
cholesterol metabolic process	1
C21-steroid hormone metabolic process	1
regulation of biological quality	1

Indications & clinical

Indications

5 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
Lennox-Gastaut syndrome	3	MONDO:0016532	MONDO:0016532
complex regional pain syndrome	2	MONDO:0019369	EFO:1001998
epilepsy	1	MONDO:0005027	EFO:0000474
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: 21.

Phase distribution

Phase	Trials
PHASE1	12
PHASE3	4
PHASE2	4
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04938427	PHASE3	COMPLETED	A Study of Soticlestat as an Add-on Therapy in Children, Teenagers, and Adults With Lennox-Gastaut Syndrome
NCT04940624	PHASE3	COMPLETED	A Study of Soticlestat as an Add-on Therapy in Children and Young Adults With Dravet Syndrome
NCT05163314	PHASE3	TERMINATED	A Study of Soticlestat as an Add-on Therapy in Children and Adults With Dravet Syndrome or Lennox-Gastaut Syndrome
NCT06422377	PHASE3	TERMINATED	A Study Evaluating Soticlestat in Participants With Dravet Syndrome or Lennox-Gastaut Syndrome Who Have Been Exposed to Fenfluramine
NCT03166215	PHASE1/PHASE2	COMPLETED	Study of TAK-935 as an Adjunctive Therapy in Participants With Developmental and/or Epileptic Encephalopathies
NCT03635073	PHASE2	TERMINATED	A Study of Soticlestat in Adults and Children With Rare Epilepsies
NCT03650452	PHASE2	COMPLETED	A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy, Safety, and Tolerability of TAK-935 (OV935) as an Adjunctive Therapy in Pediatric Participants With Developmental and/or Epileptic Encephalopathies
NCT03694275	PHASE2	COMPLETED	A Multicenter, Open-label, Pilot Study of Soticlestat (TAK-935/OV935) in Participants With 15Q Duplication Syndrome (Dup 15q) or Cyclin-Dependent Kinase-Like 5 (CDKL5) Deficiency Disorder (ARCADE STUDY)
NCT03990649	PHASE2	COMPLETED	Study of TAK-935 as an Adjunctive Therapy in Adult Participants With Complex Regional Pain Syndrome (CRPS)
NCT02201056	PHASE1	COMPLETED	Safety, Tolerability, and Pharmacokinetics of Escalating Single Doses of TAK-935
NCT02497235	PHASE1	COMPLETED	A Phase 1 Positron Emission Tomography Study to Measure Cholesterol 24S-Hydroxylase Target Occupancy of TAK-935
NCT02539134	PHASE1	COMPLETED	TAK-935 Multiple Rising Dose Study in Healthy Participants
NCT02906813	PHASE1	COMPLETED	A Study to Determine the Bioavailability and Food Effect of a Single TAK-935 Dose in Healthy Participants
NCT04461483	PHASE1	COMPLETED	A Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Single Ascending Dose and Multiple Doses With Titration of TAK-935 in Healthy Japanese Participants
NCT04992442	PHASE1	COMPLETED	Study to Assess Absolute Bioavailability of TAK-935 (OV935) and to Characterize Mass Balance, Pharmacokinetics, Metabolism, and Excretion of [14C]TAK-935 (OV935) in Healthy Male Participants
NCT05064449	PHASE1	COMPLETED	A Study of Soticlestat With Itraconazole and Mefenamic Acid in Healthy Adults
NCT05098041	PHASE1	COMPLETED	A Study of Soticlestat and Rifampin in Healthy Adults
NCT05098054	PHASE1	COMPLETED	A Study of Soticlestat in Adults With Liver Failure Compared to Those With Normal Liver Function
NCT05284760	PHASE1	COMPLETED	A Study of Soticlestat Tablets in Healthy Adults
NCT05309902	PHASE1	WITHDRAWN	A Study of Soticlestat in Healthy Adults To Evaluate the Effect on QTc Interval
NCT05602818	PHASE1	COMPLETED	A Study of Soticlestat in Healthy Adult Nondependent Recreational Drug Users With Central Nervous System (CNS) Depressant Experience

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.

3 molecules share ≥1 primary target. Top 3 by shared-target count:

Molecule	Source	Status	Shared targets
EFAVIRENZ	ChEMBL + PubChem	Phase 4 (approved)	CYP46A1
VORICONAZOLE	ChEMBL + PubChem	Phase 4 (approved)	CYP46A1
CHOLESTEROL	ChEMBL	Phase 2	CYP46A1