同义名 :	克立咪唑 盐酸盐 ;Clemizole (hydrochloride); Allercur; AL 20; Clemizole hydrochloride
	CAS号 :	1163-36-6
	货号 :	A397957
	分子式 :	C19H21Cl2N3
	纯度 :	99%
	分子量 :	362.3
	MDL号 :	MFCD00051435
	存储条件：	Pure form Sealed in dry,2-8°C In solvent -20°C:3-6个月-80°C:12个月
	溶解度 :	-
	动物实验配方：

生物活性

描述

Clemizole HCl, 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. 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 decreased hERG current by blocking both open and closed states of the channel in a concentration-dependent manner (IC50 : 0.07 μM). Clemizole also moderately decreased IKs and human Kv 1.5 channel current. Moreover, clemizole increased the duration of the ventricular action potential in guinea pig hearts and the QTc interval in isolated perfused hearts from guinea pigs, in a concentration-dependent manner (0.1-1.0 μM)[2]. Clemizole HCl 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].

临床研究
NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
NCT00945880	Hepatitis C	Phase 1	Completed	-	-
NCT03069508	Hepatocellular Carcinoma	Phase 2	Enrolling by invitation	January 31, 2018	Turkey ... 展开 >> University of Ankara Ankara, Turkey 收起 <<

实验方案
	1mg	5mg	10mg
1 mM 5 mM 10 mM	2.76mL 0.55mL 0.28mL	13.80mL 2.76mL 1.38mL	27.60mL 5.52mL 2.76mL

参考文献

[1]Einav S, Gerber D, Bryson PD, Sklan EH, Elazar M, Maerkl SJ, Glenn JS, Quake SR. Discovery of a hepatitis C target and its pharmacological inhibitors by microfluidic affinity analysis. Nat Biotechnol. 2008 Sep;26(9):1019-27 [2]Jie LJ, Wu WY, Li G, Xiao GS, Zhang S, Li GR, Wang Y. Clemizole hydrochloride blocks cardiac potassium currents stably expressed in HEK 293 cells. Br J Pharmacol. 2017 Feb;174(3):254-266 [3]Nishimura T, Hu Y, Wu M, Pham E, Suemizu H, Elazar M, Liu M, Idilman R, Yurdaydin C, Angus P, Stedman C, Murphy B, Glenn J, Nakamura M, Nomura T, Chen Y, Zheng M, Fitch WL, Peltz G. Using chimeric mice with humanized livers to predict human drug metabolism and a drug-drug interaction. J Pharmacol Exp Ther. 2013 Feb;344(2):388-96 [4]Jie LJ, Wu WY, Li G, Xiao GS, Zhang S, Li GR, Wang Y. Clemizole hydrochloride blocks cardiac potassium currents stably expressed in HEK 293 cells. Br J Pharmacol. 2017 Feb;174(3):254-266 [5]Nishimura T, Hu Y, Wu M, Pham E, Suemizu H, Elazar M, Liu M, Idilman R, Yurdaydin C, Angus P, Stedman C, Murphy B, Glenn J, Nakamura M, Nomura T, Chen Y, Zheng M, Fitch WL, Peltz G. Using chimeric mice with humanized livers to predict human drug metabolism and a drug-drug interaction. J Pharmacol Exp Ther. 2013 Feb;344(2):388-96