PROTACpan-KRAS degrader-1 is a pan-KRAS PROTAC degrader that targets multiple KRAS mutants, including G12D, G12C, G12V, and G13D. It effectively degrades the KRAS mutant (G12D) in AGS cells, with a DC50 of 1.1 nM and a Dmax of 95%. This compound can be used in studies of diseases caused by KRAS mutations or amplifications, particularly in cancers such as breast, bladder, and gastric cancer.

KRas (G12D):1.1 nM (DC50)

PROTAC pan-KRAS degrader-1 (Compound 144) significantly inhibits cell proliferation across various KRAS mutation types in AGS, SW620, AsPC-1, H358, HCT116, and MKN-1 cells within the range of 0.31-20000 nM over 96 hours, with IC50 values of 3, 10, 2.6, 5, 13, and 0.9 nM, respectively. Moreover, PROTAC pan-KRAS degrader-1, at concentrations ranging from 1.53-100000 nM, potently degrades KRAS mutation (G12D) in AGS cells, exhibiting a DC50 of 1.1 nM and a Dmax of 95%. Within 24 hours at a concentration range of 0.16-100 nM, it effectively degrades different KRAS mutations (G12D and G12V) in AGS and SW620 cells, achieving maximum degradation efficiency at 0.8 and 4 nM, respectively.