Wayne P. Bocchinfuso

TL;DR: The identification and characterization of a novel and selective PRMT5 inhibitor with potent in vitro and in vivo activity is described and compound 1 showed antitumor activity in mouse xenografts when dosed orally and can serve as an excellent probe molecule for understanding the biological function ofPRMT5 in normal and cancer cells.

TL;DR: The novel piperidinylisoxazole system LY2562175 was discovered and is a potent and selective FXR agonist in vitro and has robust lipid modulating properties, lowering LDL and triglycerides while raising HDL in preclinical species.

TL;DR: Major protection of H/D exchange was observed for some fragments in helixes 3, 7, and 8 of the ligand binding domain, regions which are similar to those seen for the natural hormone VD3.

TL;DR: Preclinical characterization of LY3537982, a novel, highly selective and potent inhibitor of the KRAS-G12C protein, discovered using structure-based design suggests that in certain biologic contexts, broader and more durable anti-tumor activity could be achieved with combination regimens.