RAS is the most frequently mutated oncogene in human cancers; however, KRAS is the most frequently mutated subtype of the RAS family (the other two members are HRAS protein and NRAS protein). Most lung cancers, pancreatic cancers, and colorectal cancers are driven by KRAS mutations. KRAS is a GTPase, a critical regulatory protein for cell survival and growth. However, due to the strong binding affinity between KRAS and GTP, and the very high failure rate for KRAS-driven cancer therapeutic study in the last 30 years, KRAS is considered as an undruggable target. With the breakthrough of KRAS (G12C)-specific covalent inhibitors in clinical trials, the undruggability of KRAS has gradually been broken.
(KRAS activity cycle)
KRAS binding with SOS1 & BAY-293 Binding with SOS1
ChemPartner’s in vitro biology team has developed assays for different screening strategies, which facilitate the identification of different types of inhibitors such as KRAS activity inhibitors and SOS1 activity inhibitors. We also conducted an in-depth study on the mechanism of inhibition.
KRAS Inhibitor Screening Strategy
The inhibitory effect of AMG-510 and BAY-293 on KRAS-wt and KRAS(G12C)