Clemizole

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

一种 H1 组胺受体拮抗剂，通过抑制 NS4B 的 RNA 结合来显着抑制 HCV 复制 (IC50=24 nM)，对宿主细胞毒性很小。

An H1 histamine receptor antagonist that substantially inhibits HCV replication by suppression of NS4B's RNA binding (IC50=24 nM) with little toxicity for the host cells; also selectively and efficiently blocks TRPC5 currents and Ca(2+) entry with IC50 of 1-1.3 uM, 6-fold selectivity over TRPC4β (IC50 = 6.4 μM), and almost 10-fold selectivity over TRPC3 (IC50 =9.1 uM) and TRPC6 (IC50=11.3 uM), only very weakly affects TRPM3, TRPM8 and TRPV1, V2, V3, and V4 channels. HCV Infection Phase 2 Clinical(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). 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.(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.

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). 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.

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.

Clemizole | NSC 46261 | NSC-46261 | NSC46261

Membrane Transporter/Ion Channel

TRP/TRPV Channel

NS4BH1histaminereceptor

Infection

HCV Infection

442-52-4

325.8352

C19H20ClN3

>98% (HPLC)

10 mM in DMSO

ClC1=CC=C(C=C1)CN2C3=CC=CC=C3N=C2CN4CCCC4

1H-Benzimidazole, 1-[(4-chlorophenyl)methyl]-2-(1-pyrrolidinylmethyl)-

(-20℃)

With Ice Pack

≥ 2 years