CH 223191

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.