Kirsten Rat Sarcoma Virus Homolog G12C Mutant (KRAS G12C)

The Kirsten rat sarcoma viral oncogene homolog (KRAS) G12C mutant is a constitutively active form of the K-Ras GTPase due to a glycine-to-cysteine substitution at codon 12. This mutation locks KRAS in an active state, leading to continuous activation of downstream signaling pathways such as RAF-MEK-ERK and PI3K-AKT-mTOR, driving uncontrolled cell proliferation and survival. It is a significant therapeutic target in cancers, particularly NSCLC, and is addressed by direct covalent inhibitors like sotorasib and adagrasib.

Other names

KRAS G12C MutantKRAS G12CK-Ras G12C

Covalent inhibition of KRAS G12C mutant protein, locking it in an inactive conformation