1-[(4-氯苯基)甲基]-2-(吡咯烷-1-基甲基)苯并咪唑盐酸盐

IC50: 24 nM (NS4B)
H1 histamine receptor

Clemizole hydrochloride is found to inhibit HCV RNA replication in cell culture that is mediated by its suppression of NS4B’s RNA binding, with little toxicity for the host cell. The EC ₅₀ of Clemizole on the W55R mutant J6/JFH RNA is ~18 µM (2.25 times the EC ₅₀ of the wild-type RNA). Clemizole is a novel inhibitor of TRPC5 channels. Clemizole efficiently blocks TRPC5 currents and Ca ²⁺ entry in the low micromolar range (IC ₅₀ =1.0-1.3 µM). Clemizole exhibits a six-fold selectivity for TRPC5 over TRPC4β (IC ₅₀ =6.4 µM), the closest structural relative of TRPC5, and an almost 10-fold selectivity over TRPC3 (IC ₅₀ =9.1 µM) and TRPC6 (IC ₅₀ =11.3 µM). Clemizole hydrochloride as a novel blocker of TRPC5 with a half-maximal inhibitory concentration of 1.1 µM. The concentration-response curves confirmed a concentration-dependent block of TRPC5 by Clemizole and revealed an apparent IC ₅₀ of 1.1±0.04 µM.

Clemizole hydrochloride has an unexpectedly short plasma half-life (measured at 0.15 hours); it is very rapidly biotransformed into a glucuronide (M14) and a dealkylated metabolite (M12) and into a variety of lesser metabolites in C57BL/6J mice.