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Updated: Mar 24, 2026

Fully Processed Recombinant KRAS4b: Isolating and Characterizing the Farnesylated and Methylated Protein
Published on: January 16, 2020
Progress on Covalent Inhibition of KRAS(G12C)
Kenneth D Westover1, Pasi A Jänne2, Nathanael S Gray3
1Departments of Biochemistry and Radiation Oncology, The University of Texas Southwestern Medical Center at Dallas, Dallas, Texas. kenneth.westover@utsouthwestern.edu.
Abstract:
Recent reports of small-molecule approaches to directly inhibit oncogenic KRAS(G12C) have invigorated the RAS research community by raising the possibility of drugging a protein that was long considered "undruggable." A new iteration of covalent compounds targeting the allosteric switch II pocket of KRAS(G12C) showed improved potency and selectivity and enabled studies demonstrating that KRAS(G12C) rapidly cycles its nucleotide substrate. This report illustrates the value of chemical probes in dissecting RAS biology and raises additional hope for development of viable pharmacologic strategies for directly targeting KRAS(G12C).
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