soticlestat   Click here for help

GtoPdb Ligand ID: 11517

Synonyms: OV935 | TAK-935
PDB Ligand
Compound class: Synthetic organic
Comment: Soticlestat (TAK-935, previously OV935) is a first-in-class, clinical stage, orally administered cholesterol 24-hydroxylase (CYP46A1) inhibitor. It is being investigated as a novel anti-epileptic modality for pediatric forms of epilepsy [3], such as Dravet syndrome [1,4] and Lennox-Gastaut syndrome [5]. Cholesterol 24-hydroxylase is a brain-specific enzyme (in humans) that converts cholesterol to 24S-hydroxycholesterol. 24S-hydroxycholesterol acts as a positive allosteric modulator of N-methyl-D-aspartate (NMDA) receptors. Soticlestat blocks 24S-hydroxycholesterol production in the brain in an in vivo mouse model [2].
Click here for help
2D Structure
Click here for help
Click here for structure editor
Physico-chemical Properties
Click here for help
Hydrogen bond acceptors 5
Hydrogen bond donors 1
Rotatable bonds 5
Topological polar surface area 66.32
Molecular weight 373.18
XLogP 2.79
No. Lipinski's rules broken 0
Click here for help
Canonical SMILES O=C(c1cccnc1c1ccncc1)N1CCC(CC1)(O)Cc1ccccc1
Isomeric SMILES O=C(c1cccnc1c1ccncc1)N1CCC(CC1)(O)Cc1ccccc1
InChI InChI=1S/C23H23N3O2/c27-22(20-7-4-12-25-21(20)19-8-13-24-14-9-19)26-15-10-23(28,11-16-26)17-18-5-2-1-3-6-18/h1-9,12-14,28H,10-11,15-17H2
No information available.
Summary of Clinical Use Click here for help
The first report of soticlestat's safety, tolerability, pharmacokinetics, pharmacodynamics and bioavailability (in healthy volunteers) was published in 2021 [6]. It has been progressed to larger clinical trials to determine efficacy in a range of developmental and/or epileptic encephalopathies.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT02906813 A Study to Determine the Bioavailability and Food Effect of a Single TAK-935 Dose in Healthy Participants Phase 1 Interventional Takeda 6
NCT02201056 Safety, Tolerability, and Pharmacokinetics of Escalating Single Doses of TAK-935 Phase 1 Interventional Takeda 6
NCT03650452 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 Phase 2 Interventional Takeda
NCT03635073 A Phase 2, Prospective, Interventional, Open-Label, Multi-Site, Extension Study to Assess the Long-Term Safety and Tolerability of TAK-935 (OV935) as Adjunctive Therapy in Patients With Rare Epilepsy Phase 2 Interventional Takeda
NCT03166215 Study of TAK-935 as an Adjunctive Therapy in Participants With Developmental and/or Epileptic Encephalopathies Phase 1/Phase 2 Interventional Takeda
NCT03990649 Study of TAK-935 as an Adjunctive Therapy in Adult Participants With Complex Regional Pain Syndrome (CRPS) Phase 2 Interventional Takeda