Rat sarcoma virus oncogene homolog (Ras) (Ras)

Ras proteins are small GTPases that function as molecular switches in cellular signaling, cycling between an inactive GDP-bound state and an active GTP-bound state [Wikipedia, NIH]. They are critical for regulating pathways like MAPK and PI3K, which control cell growth, survival, and differentiation [Dana-Farber, NIH]. Mutations in Ras genes, particularly KRAS, HRAS, and NRAS, are among the most common drivers of human cancer, occurring in approximately 20-30% of all tumors [NIH, BMJ]. These mutations typically lock the protein in a constitutively active state, leading to uncontrolled cell proliferation [Dana-Farber, NIH]. Historically considered "undruggable" due to the lack of traditional binding pockets, recent breakthroughs have led to the development of allele-specific inhibitors like sotorasib and adagrasib, which target the KRAS G12C mutation [BMJ, NIH].

Other names

KRASHRASNRASp21 RasRas GTPaseKirsten rat sarcoma virus oncogene homologHarvey rat sarcoma virus oncogene homologNeuroblastoma RAS viral oncogene homolog

Covalent inhibition of the inactive GDP-bound state of mutant Ras proteins (specifically G12C), allosteric inhibition of the switch II pocket, and inhibition of farnesyltransferase to prevent membrane localization.