The GTP-ase K-Ras represents the most frequently altered oncogene in cancer patients. Directly targeting K-Ras is difficult due to its picomolar affinity for GTP/GDPand the absence of easily identifiable allosteric sites. I will describe the discovery of small molecules that covalently bind to a common oncogenic mutant, K-RasG12C. These compounds have served as a blueprint for the development of multiple K-RasG12C drugs currently undergoing clinical investigation. I will also discuss ways to leverage immune cell killing of K-RasG12C cells treated with the small molecule inhibitors of K-RasG12C. I will also discuss new chemical strategies for targeting another frequent K-Ras oncogenic allele, K-RasG12D.

Award Address (Alfred Bader Award in Bioinorganic or Bioorganic Chemistry sponsored by the Alfred R. Bader Fund) Small Molecule Enabled Immune Targeting of the Oncogene K-Ras(G12C)

ACS Fall 2020 Virtual Meeting

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