CH223191

CH223191 is a synthetic small molecule antagonist of the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor. It acts as a **ligand-selective antagonist**, preferentially inhibiting halogenated aromatic hydrocarbons (HAHs) such as TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) while showing limited or no antagonism against polycyclic aromatic hydrocarbons (PAHs), synthetic flavonoids, and indirubin[1][4]. CH223191 competitively binds to the AhR ligand binding pocket with IC₅₀ values ranging from approximately 30 nM to 3.1 μM depending on the cell line and species[1][3]. The compound inhibits AhR-dependent gene expression by preventing ligand-dependent AhR nuclear translocation and transformation, rather than affecting DNA binding of already-transformed AhR complexes[1]. In vivo studies demonstrate that CH223191 reduces hepatic cytochrome P450 1A1 expression and mitigates TCDD-induced toxic effects including elevated plasma AST and ALT levels[3]. The compound has also shown beneficial effects on cortical bone mass and skeletal muscle in aged mice, with increased cortical bone volume and reduced oxidative stress in muscle tissue[2]. CH223191 serves as a valuable research tool for investigating AhR signaling pathways and dioxin toxicity.