AHR antagonist 5 free base is a selective and orally active aryl hydrocarbon receptor (AHR) inhibitor. AHR antagonist 5 free base effectively blocks AHR from translocating from the cytoplasm to the nucleus. AHR antagonist 5 free base is highly selective for AHR over other receptors, transporters, and kinases[1].
AHR antagonist 5 free base (Compound A) potently inhibits AHR activity in human and rodent cell lines (IC50 of ~35-150 nM). In human T cell assays, AHR antagonist 5 free base induces an activated T cell state. AHR antagonist 5 free base inhibits CYP1A1 and interleukin (IL)-22 gene expression and leads to an increase in pro-inflammatory cytokines, such as IL-2 and IL-9[1].
AHR antagonist 5 free base (Compound A) has been evaluated in a series of pharmacological, single-dose and repeated-dose toxicological studies in rodent and non-rodent species including 28-day Good Laboratory Practice (GLP) studies in rat and monkeys. All changes are resolved or resolving after 2 weeks of dosing cessation, except for the testicular changes in rats[1].
[1]. Marta Sanchez-Martin, et al. Ahr inhibitors and uses thereof. WO2021142180A1.