GNF351

GNF351 is a potent AhR (aryl hydrocarbon receptor) antagonist. Aryl hydrocarbon receptor (AhR) is a ligand-dependent nuclear receptor that functions as a transcription factor. It can follow a canonical signaling pathway where binding of ligands to the cytosolic AhR induces the formation of a complex that translocates to the nucleus where it dimerizes with ARNT (AhR translocator) and binds to XRE (xenobiotic response elements). In addition, it functions in non-canonical pathways involved in immune responses, inflammation, and pathology. Non-canonical signaling pathways involve competition for ARNT, binding to other partners, proteosomal degradation, and/or activation of pathways when in the cytosol, and synergy with other regulatory gene sequences. AhR plays critical roles, functioning as a sensor to the environment, and can respond to POPs (persistent organic pollutants) and other stressors. Its activation can result in the accumulation of toxic metabolic intermediates and liver toxicity, developmental issues, neurotoxicity, amongst others. It also plays a role in cancer, acting as suppressor or promoter in a context-dependent mode. Its contribution to immunoregulation has made it an attractive therapeutic target. Antagonists are being investigated in the cancer therapy field, while agonists play prove useful in inflammatory disorders.