Discovery of Soticlestat (TAK-935) , a First-in-class Drug for Antiseizure Medication (ASM)

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  • 小児難治性てんかん治療薬soticlestat（TAK-935）の創製

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Description

Cholesterol 24-hydroxylase (CH24H, CYP46A1) is a brain-specific CYP enzyme that plays a role in the homeostasis of brain cholesterol by converting cholesterol to 24S-hydroxycholesterol (24HC) . The therapeutic potential of CH24H inhibition had been underexploited partly because of the lack of selective inhibitor reported thus far. In our research to discover CH24H inhibitor based on structure-based drug design (SBDD) , soticlestat was identified as a highly potent CH24H inhibitor with high selectivity over off-target CYPs. Oral administration of soticlestat significantly reduced the seizure frequency in multiple animal models of epilepsy, which led us to develop a CH24H inhibitor for treatment of developmental and epileptic encephalopathies (DEE) . Soticlestat is currently being investigated as a drug for treatment of Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS) with a novel mechanism of action.

Journal

  • MEDCHEM NEWS

    MEDCHEM NEWS 33 (2), 64-69, 2023-05-01

    The Pharmaceutical Society of Japan

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