Qiuping Ye

TL;DR: The discovery of AM-8553, a potent and selective piperidinone inhibitor of the MDM2-p53 interaction, led to the discovery of a one-carbon tethered sulfone which gave rise to substantial improvements in biochemical and cellular potency.

TL;DR: Optimization afforded AM-8553, a potent and selective MDM2 inhibitor with excellent pharmacokinetic properties and in vivo efficacy, and the discovery of novel inhibitors of theMDM2-p53 protein-protein interaction.

TL;DR: Novel non-nucleoside inhibitors of the HCV RNA polymerase (NS5b) with sub-micromolar biochemical potency have been identified which are selective for the inhibition of HCV NS5b over other polymerases.

TL;DR: Therapeutic combination studies of AMG 232 with chemotherapies that induce DNA damage and p53 activity resulted in significantly superior antitumor efficacy and regression, and markedly increased activation of p53 signaling in tumors.

TL;DR: Within this morpholinone series, AM-8735 emerged as an inhibitor with remarkable biochemical potency and cellular potency, as well as pharmacokinetic properties, and shows excellent antitumor activity in the SJSA-1 osteosarcoma xenograft model.