KRAS protein (KRAS)

KRAS (Kirsten rat sarcoma viral oncogene homolog) is a small GTPase protein that plays a central role in regulating cell proliferation, differentiation, and survival. It acts as a molecular switch within the cell, cycling between an inactive GDP-bound state and an active GTP-bound state. The KRAS gene is one of the most frequently mutated oncogenes in human cancers, with mutations—such as the G12C variant—being particularly relevant in lung adenocarcinoma, pancreatic ductal carcinoma, colorectal cancer, and other malignancies. When mutated at codon 12—as in KRAS(G12C)—the protein's intrinsic ability to hydrolyze GTP is impaired or altered. This leads to persistent activation of downstream signaling pathways promoting uncontrolled cell growth—a hallmark of cancer. Recent drugs such as MRTX849 selectively bind covalently to Cys^12 on mutant KRAS(G12C), locking it into its inactive GDP-bound state and inhibiting aberrant signaling. This has opened new avenues for targeted therapy against previously "undruggable" RAS-driven cancers.

Other names

Kirsten rat sarcoma viral oncogene homologc-K-RASKi-RasKRAS2RASK2

Covalent inhibition of KRAS(G12C)