Kirsten Rat Sarcoma Viral Oncogene Homolog G12C Mutant Protein (KRAS G12C)

The Kirsten rat sarcoma viral oncogene homolog (KRAS) G12C mutant protein is a constitutively active GTPase that drives uncontrolled cell growth and survival in various cancers. The G12C mutation, where glycine is replaced by cysteine at codon 12, impairs GTP hydrolysis, leading to persistent activation of downstream signaling pathways like RAF-MEK-ERK and PI3K-AKT-mTOR. This mutant form is a therapeutic target, with covalent inhibitors like sotorasib and adagrasib designed to specifically bind the cysteine residue and inhibit its activity. It is frequently found in NSCLC and other cancers.

Other names

KRAS G12C MutantKRAS G12CK-Ras G12CG12C KRAS

Covalent inhibitors irreversibly bind to the mutant cysteine residue at position 12, inhibiting KRAS-G12C activity.