Kirsten rat sarcoma viral oncogene homolog (KRAS) G12D mutant (KRAS G12D)

The KRAS G12D mutation is a common activating mutation in the KRAS gene, where glycine at codon 12 is replaced by aspartic acid. This mutation impairs GTP hydrolysis, locking KRAS in its active state and constitutively activating downstream signaling pathways like RAF-MEK-ERK and PI3K-AKT-mTOR, driving uncontrolled cell growth and survival. It is prevalent in cancers such as pancreatic ductal adenocarcinoma, colorectal cancer, and lung adenocarcinoma. Recent structural studies have identified that selective inhibitors can target specific conformations unique to mutant forms like KRAS(G12D), such as the switch II pocket.

Other names

KRAS(G12D)KRAS p.Gly12AspKRAS G12D mutant

Inhibition of KRAS G12D mutant by targeting the switch II pocket.