Sang Min Lim

TL;DR: Findings suggest that gain-of-function mutations in DDR2 are important oncogenic events and are amenable to therapy with dasatinib, and provide a rationale for designing clinical trials with the FDA-approved drug d asatinib in patients with lung SCCs.

TL;DR: These first-in-class covalent K-Ras inhibitors demonstrate that irreversible targeting of the K- Ras guanine-nucleotide binding site is potentially a viable therapeutic strategy for inhibition of Ras signaling.

TL;DR: High-resolution in situ proteomic-based chemical profiling of SML demonstrates that SML is highly selective for K-Ras G12C over other small GTPases, and high-resolution conservation analysis of the Ras family GN-binding pocket reveals variability in the side chains surrounding the active site and adjacent regions, especially in the switch I region.

TL;DR: The discovery of difluoromethylene bisphosphonate analogues such as compound 11, which, despite exhibiting reduced efficiency as covalent G12C KRAS inhibitors, remove the liability of the hydrolytic instability of the diphosphate moiety present in SML-8-73-1 and provide the foundation for development of prodrugs to facilitate cellular uptake.

TL;DR: The structure-based medicinal chemistry effort that resulted in the discovery of the first selective irreversible Her3 ligand that forms a covalent bond with cysteine 721 which is unique to Her3 among all kinases is reported on.