Covalent hits on KRAS

University of California, San Francisco- and Harvard Medical School-led teams have independently synthesized the first covalent inhibitors of a common oncogenic form of KRAS.^1,2 Araxes Pharma LLC has licensed the UCSF team's findings and has partnered with Johnson & Johnson to optimize the compounds for in vivo testing.

Ras proteins are GTPases that act as molecular switches to control cell growth in response to extracellular signals. Three genes encode related Ras proteins: KRAS (K-Ras), v-Ha-ras Harvey rat sarcoma viral oncogene homolog (HRAS) and neuroblastoma Ras viral (v-Ras) oncogene (NRAS). Activating mutations in these genes are found in about 30% of cancers...