tcsc1489 Clemizole (hydrochloride)

Clemizole hydrochloride is an H1 histamine receptor antagonist, is found to substantially inhibit HCV replication. The IC₅₀ of Clemizole for RNA binding by NS4B is 24±1 nM, whereas its EC₅₀ for viral replication is 8 µM.



IC50 & Target: IC50: 24 nM (NS4B)^[1]
H1 histamine receptor^[1]

In Vitro: 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 EC₅₀ of Clemizole on the W55R mutant J6/JFH RNA is ~18 µM (2.25 times the EC₅₀ of the wild-type RNA)^[1]. Clemizole is a novel inhibitor of TRPC5 channels. Clemizole efficiently blocks TRPC5 currents and Ca²⁺ entry in the low micromolar range (IC₅₀=1.0-1.3 µM). Clemizole exhibits a six-fold selectivity for TRPC5 over TRPC4β (IC₅₀=6.4 µM), the closest structural relative of TRPC5, and an almost 10-fold selectivity over TRPC3 (IC₅₀=9.1 µM) and TRPC6 (IC₅₀=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 IC₅₀ of 1.1±0.04 µM^[2].

In Vivo: 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^[3].