Ao Zhang

Dean, College of Pharmaceutical Sciences

Shang Hai Jiao Tong University

Short Biography

Ao Zhang is currently a Distinguished Professor and Dean of School of Pharmaceutical Sciences at Shanghai Jiao Tong University, Shanghai, China. His research interests are focused on small molecule drug discovery based on medicinal chemical biology. He has co-authored over 200 publications in prestigious journals and holds over 100 patents.

Presentation Topic: Targeting Undruggable KRAS: Past, present, and Future
RAS proteins are members of small protein GTPase families encoded by three human RAS genes (KRAS, HRAS and NRAS), among which, KRAS is the most commonly altered one in human cancers. KRAS acts as a molecular switch that cycles between a GTP bound ‘‘on’’ state and a GDP bound ‘‘off’’ state that regulates many signaling cascades to maintain essential physiological functions of cells, which mainly include RAF-MEK-ERK, PI3K-AKT, and RALGDS-RAL. Disruption of the on-off balance by KRAS mutations has been the main course of many diseases, especially cancer. KRAS has long been an undruggable target until the successful launch of the two irreversible covalent inhibitors MRTX849 and AMG510 targeting KRASG12C for non-small cell lung cancer in 2021. This breakthrough not only breaks the KRAS-undruggable curse, but also makes the other KRAS mutations (G12D, G12V, G12S…) druggable as well. This talk will speak on the advances in the drug discovery of targeted KRAS inhibitors. Meanwhile, our own effects on design of KRAS G12D mutant selective and G12C/G12D pan-inhibitors/degraders will be discussed as well.