MCB-36 is a versatile KRAS-targeting PROTAC degrader recruiting the VHL protein without affecting KRAS transcription. It exerts minimal impact on HRAS and NRAS protein levels. MCB-36 binds with high affinity (Kd ~ 1 pM) to G12D, G12C, G12V, and wild-type KRAS in the GDP-loaded state. By reducing p-ERK levels, MCB-36 induces apoptosis (apoptosis). It effectively inhibits cancer cells resistant to KRASG12C and remodels the tumor immune microenvironment. MCB-36 is applicable in research on colorectal and lung cancer.
