Soticlestat is an inhibitor of cholesterol 24-hydroxylase/CYP46A1 (IC50 = 0.0074 ?M).1 It is selective for cholesterol 24-hydroxylase/CYP46A1 over the cytochrome P450 (CYP) isoforms CYP2C8, -2C9, -2D6, -3A4, -1A2, and 2C19 (IC50s = 62, 19, >100, 66, >100, and 14 ?M, respectively). Soticlestat (0.02% in the diet) reduces seizure frequency and severity and improves survival in a model of Dravet syndrome induced by hyperthermia in mice with heterozygous deletion of Scn1a (Scn1a+/-), the gene encoding voltage-gated sodium channel 1.1 (Nav1.1).2
1.Koike, T., Yoshikawa, M., Ando, H.K., et al.Discovery of soticlestat, a potent and selective inhibitor for cholesterol 24-hydroxylase (CH24H)J. Med. Chem.64(16)12228-12244(2021) 2.Hawkins, N.A., Jurado, M., Thaxton, T.T., et al.Soticlestat, a novel cholesterol 24-hydroxylase inhibitor, reduces seizures and premature death in Dravet syndrome miceEpilepsia62(11)2845-2857(2021)