CS-1036

CS-1036 (also known as DS-1036) is an orally bioavailable small molecule agonist of the Free fatty acid receptor 1 (FFAR1), also known as GPR40, which was under development by Daiichi Sankyo for the treatment of type 2 diabetes mellitus. FFAR1 is a G protein-coupled receptor predominantly expressed in pancreatic beta cells; its activation by long-chain fatty acids or synthetic agonists enhances glucose-stimulated insulin secretion (GSIS). This mechanism is therapeutically attractive because it potentially offers glycemic control with a low risk of hypoglycemia, as the insulinotropic effect is dependent on elevated blood glucose levels. CS-1036 reached Phase 1 and Phase 2 clinical trials, where its safety, tolerability, and pharmacokinetics were evaluated. However, Daiichi Sankyo discontinued the development of CS-1036, likely reflecting the broader challenges faced by the GPR40 agonist class, including concerns over idiosyncratic hepatotoxicity observed with other candidates in the same category.