CH 223191 is an effective and specific antagonist of the aryl hydrocarbon receptor (AhR), capable of inhibiting TCDD-mediated AhR nuclear translocation and DNA binding, and suppresses TCDD-induced luciferase activity, with an IC50 of 0.03 μM[1]. CH-223191 effectively prevents TCDD-induced cytochrome P450 induction, hepatotoxicity, and wasting syndrome in mice.
In vitro, CH 223191 (0.1-10 μM; pre-treated for 1 hour) inhibits TCDD-induced cytochrome P450 1A1 mRNA expression in a dose-dependent manner[1]. CH 223191 reduces the invasiveness of the LNT-229 cell line by 81% and the LN-308 cell line by 72%[2]. Pre-treatment with CH 223191 (10–6 M) significantly reverses the inhibition effect of TCDD (10–9 M) on human AChE promoter activity[3].
In vivo, CH 223191 (10 mg/kg; once daily; for 25 days) inhibits the expression of cytochrome P450 1A1 in the liver of mice treated with TCDD and reduces hepatic fat content, lowering AST and ALT activity[1].
References:
[1] Kim SH, et al. Novel compound 2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazo-phenyl)-amide (CH-223191) prevents 2,3,7,8-TCDD-induced toxicity by antagonizing the aryl hydrocarbon receptor. Mol Pharmacol. 2006 Jun;69(6):1871-8.
[2] Gramatzki D , Pantazis G , Schittenhelm J ,et al. Aryl hydrocarbon receptor inhibition downregulates the TGF-beta/Smad pathway in human glioblastoma cells[J]. Oncogene. 2009(28).
[3] Xie, Heidi Qunhui,Xu, Hai-Ming,Fu, Hua-Ling,et al. AhR-Mediated Effects of Dioxin on Neuronal Acetylcholinesterase Expression in Vitro[J].Environmental Health Perspectives, 2013, 121.
CH 223191是一种有效且特异性的芳烃受体（AhR）拮抗剂，可抑制TCDD介导的AhR核转位和DNA结合，并抑制TCDD诱导的荧光素酶活性，IC50为0.03 μM[1]。CH-223191可有效预防TCDD诱导的细胞色素P450诱导、肝毒性和小鼠消瘦综合征。
在体外，CH 223191（0.1-10 μM;预处理1小时）以剂量依赖性方式抑制TCDD诱导的细胞色素P450 1A1 mRNA表达[1]。CH 223191使LNT-229细胞系的侵袭性降低81%，使LN-308细胞系的侵袭性降低72%[2]。CH 223191（10–6 M）预处理显著逆转了TCDD（10–9 M）对人AChE启动子活性的抑制作用[3]。
在体内，CH 223191（10 mg/kg;每日一次; 25天）可抑制TCDD给药小鼠肝脏中细胞色素P450 1A1的表达和肝细胞内脂肪含量，降低AST和ALT活性[1]。