AR420626

AR420626 is a **selective small-molecule agonist** of the GPR41 (free fatty acid receptor 3; FFAR3) receptor. It has demonstrated **anti-tumor activity in preclinical hepatocellular carcinoma (HCC) models** by inducing apoptosis in HCC cells, via a mechanism involving upregulation of TNF-α expression and **inhibition of histone deacetylases (HDACs)**, especially class II HDACs. This results in increased histone H3 acetylation, changes in chromatin structure, and upregulation of pro-apoptotic genes. AR420626 also activates the mTORC1 pathway and enhances proteasome-mediated degradation of HDACs. The drug’s **mechanism is dependent on GPR41/FFA3 activation**, with observed efficacy in HepG2 and HLE cell models and significant tumor suppression in HepG2 xenograft mouse models. The molecule has also been reported to modulate gastrointestinal function and peptide YY release in prior studies[1][2][3].