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].
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2D Structure
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Physico-chemical Properties
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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
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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
1. Miziak B, Czuczwar S. (2021)
Advances in the design and discovery of novel small molecule drugs for the treatment of Dravet Syndrome.
Expert Opin Drug Discov, 16 (5): 579-593. [PMID:33275464]
2. Nishi T, Kondo S, Miyamoto M, Watanabe S, Hasegawa S, Kondo S, Yano J, Watanabe E, Ishi T, Yoshikawa M et al.. (2020)
Soticlestat, a novel cholesterol 24-hydroxylase inhibitor shows a therapeutic potential for neural hyperexcitation in mice.
Sci Rep, 10 (1): 17081. [PMID:33051477]
3. Perry MS. (2020)
New and Emerging Medications for Treatment of Pediatric Epilepsy.
Pediatr Neurol, 107: 24-27. [PMID:31980296]
4. Strzelczyk A, Schubert-Bast S. (2020)
Therapeutic advances in Dravet syndrome: a targeted literature review.
Expert Rev Neurother, 20 (10): 1065-1079. [PMID:32799683]
5. Strzelczyk A, Schubert-Bast S. (2021)
Expanding the Treatment Landscape for Lennox-Gastaut Syndrome: Current and Future Strategies.
CNS Drugs, 35 (1): 61-83. [PMID:33479851]
6. Wang S, Chen G, Merlo Pich E, Affinito J, Cwik M, Faessel H. (2021)
Safety, tolerability, pharmacokinetics, pharmacodynamics, bioavailability and food effect of single doses of soticlestat in healthy subjects.
Br J Clin Pharmacol, 87 (11): 4354-4365. [PMID:33837574]