Stiripentol

Stiripentol (STP) is an anticonvulsant agent, which can inhibit N-demethylation of CLB to NCLB mediatated by CYP3A4 (noncompetitively) and CYP2C19 (competitively) with K_i of 1.59±0.07 and 0.516±0.065 μM and IC₅₀ of 1.58 and 3.29 μM, respectively. IC50 & Target: IC50: 1.58 μM (CYP3A4), 3.29 μM (CYP2C19)^[1]
Ki: 1.59±0.07μM (CYP3A4), 0.516±0.065 μM (CYP2C19)^[1] In Vitro: Stiripentol (STP) is an anticonvulsant agent, which can inhibit N-demethylation of CLB to N-desmethylclobazam (NCLB) mediated by CYP3A4 (noncompetitively) and CYP2C19 (competitively). The inhibition of CLB demethylation by Stiripentol (STP) is best described by a noncompetitive inhibition model with apparent K_i=1.6 μM for the cDNA-expressing CYP3A4 and by a competitive inhibition model with K_i=0.52 μM for the cDNA-expressing CYP2C19. Formation of OH-NCLB from NCLB by cDNA-expressing CYP2C19 is competitively inhibited by Stiripentol (STP) with a K_i=0.14 μM^[1]. In Vivo: In mice treating with Stiripentol (STP) monotherapy, the difference between BT₁ (39.67±1.09°C) and BT₂ (41.32±1.05°C) reaches statistical significance (t=3.097, p<0.05). The difference in BT₂ between Stiripentol (STP) monotherapy and CLB monotherapy is statistically significant (t=2.615, p<0.05). In mice treating with Stiripentol (STP)+CLB combination therapy, the difference between BT₁ (40.18±0.58°C) and BT₂ (43.03±0.49°C) reaches statistical significance (t=10.44, p<0.01)^[2].