KRAS G12D (Gly12Asp) mutant protein (KRAS G12D)

KRAS G12D is a mutant form of the Kirsten rat sarcoma viral oncogene (KRAS) in which glycine at position 12 is substituted with aspartic acid (G12D). This mutation results in constitutive, oncogenic signal transduction that drives persistent proliferation and survival signals, especially in pancreatic, colorectal, and non-small cell lung cancers. INCB161734 is a novel, potent, and selective orally bioavailable small-molecule inhibitor that binds specifically to the switch II pocket of KRAS G12D, inhibiting its signaling activity, suppressing tumor cell proliferation, and inducing apoptosis in G12D-mutant cells, while sparing the wildtype protein. The drug is currently under investigation in clinical trials for multiple advanced solid tumor types harboring the KRAS G12D mutation[1][2][4].

Other names

KRAS p.G12DK-Ras p.Gly12AspKirsten rat sarcoma viral oncogene homolog G12D mutant

Inhibition of mutant KRAS G12D signaling via direct binding to the switch II pocket, impairing GDP/GTP exchange and preventing downstream activation of the ERK and PI3K pathways[1][2]