KR-pep-2D

KR-pep-2D is a macrocyclic peptide inhibitor that targets the KRAS protein, specifically exhibiting high affinity for the KRAS G12D mutant. Discovered using the RaPID (Random non-standard Peptide Integrated Discovery) system, it binds to the switch II pocket of KRAS in its active, GTP-bound state. This binding sterically hinders the interaction between KRAS and its downstream effectors, such as RAF kinases, thereby suppressing oncogenic MAPK/ERK signaling. KR-pep-2D is primarily utilized as a research tool and tool compound in preclinical studies, including therapeutic screening assays with patient-derived pancreatic cancer organoids, to evaluate the sensitivity of KRAS-mutant models to targeted inhibition.