Implications and development of AHR-based therapeutic agents

The emerging role of the AHR in modulating disease processes such as the immune and inflammatory responses, indicates a need for AHR-based investigative tools and therapeutic agents. Since the AHR has historically been aligned with the adverse biological effects of environmental contaminants, setting the stage for its potential role as a therapeutic target requires the use of a different lens through which to view its actions. This alternative perspective is enhanced by the discovery and further study of endogenous AHR agonists, "pure" AHR antagonists and unique SARMS. Towards this end, the discoveries that AHR agonists can alleviate inflammatory-induced disease severity in preclinical animal models coupled with the identification of SARMs (i.e., AL-3) identifies novel approaches to be used for treating many chronic inflammatory disease states. Further, the recent identification of an endogenous, tumor-promoting AHR agonist, when coupled with our improved understanding of the rules that govern the activities of AHR antagonists (i.e., CH223191), will likely lead to AHR antagonists with chemotherapeutic properties. These small, but significant strides represent only a glimpse of the future advances that will be made in the development of AHR-based therapeutic agents.