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Kevan Shokat

Overcoming the Undruggable Nature of The Most Common Human Oncogene K-Ras

Student Invited Lecture
Wed, Apr. 5, 2023, 4:30pm
Taylor Auditorium, Frick Chemistry Lab B02
Host: SILS

Somatic mutations in the small GTPase K-Ras are the most common activating lesions found in human cancer, and are generally associated with poor response to standard therapies. Efforts to directly target this oncogene have faced difficulties due to its picomolar affinity for GTP/GDP and the absence of known allosteric regulatory sites. I will discuss the development of small molecules that irreversibly bind to a common oncogenic mutant, K-Ras G12C. These compounds rely on the mutant cysteine for binding and therefore do not affect the wild type protein (WT). New covalent molecules targeting K-Ras G12S and G12R are currently under development and will be discussed. I will also discuss ways to leverage the immune system to overcome drug resistance.