KRAS protein (Kirsten rat sarcoma viral oncogene homolog) (KRAS)

KRAS protein is a small GTPase that acts as a molecular switch, cycling between GDP-bound inactive and GTP-bound active states, and is a central hub for signal transduction pathways regulating cell proliferation, differentiation, and survival. Mutations in the KRAS gene, frequently found at amino acid residues G12, G13, and Q61, lock KRAS in an active GTP-bound conformation, resulting in constitutive signaling and oncogenesis in a variety of human cancers. Peptides relating to mutated KRAS may refer either to the mutant forms of the KRAS protein itself or to therapeutic peptides that specifically bind to or interfere with mutant KRAS proteins, inhibiting their oncogenic function. Direct pharmacological targeting of mutant KRAS has historically been challenging, but covalent inhibitors for specific mutants (notably G12C), as well as new modalities such as peptide-based aggregation inducers, are emerging therapeutic strategies.

Other names

K-RasKRAS2v-Ki-ras2c-Ki-rasRASK2Ras-related C3 botulinum toxin substrate 4GTPase KRas

Covalent inhibition of mutant cysteine residue (G12C) to lock KRAS in inactive state (sotorasib, adagrasib) - Peptide-induced protein misfolding/aggregation - Downstream pathway inhibition (e.g., MAPK pathway blockers)