KRASG12R mutant-selective covalent inhibitor
privileged arginine-reactive functional group
from previously disclosed KRAS inhibitors
J. Am. Chem. Soc.
University of California San Francisco, San Francisco, CA
compound 3
5 mins read
Context. “Compound 3” (UCSF) is a covalent KRASG12R inhibitor used as a proof-of-concept for covalent arginine modification. KRAS is the first oncoprotein to be identified and is a well-known cancer-driving protein. As one of the most frequently mutated proteins in pancreatic and colorectal cancers, residues that are frequently mutated are known as mutant hot spots. The Shokat group has published a number of high-profile papers targeting KRAS mutants, including one targeting KRASG12S just last month. Here the group uses a cleverly designed reactive group that selectively engages with arginine, an uncommonly targeted amino acid, by using a reaction, first described in 1916, to target the arginine sidechain selectively. These advances in the field of targeting KRAS mutants come on the…
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