PRO-6E is an oral active PROTAC based on Cereblon ligand, and induces the degradation of MET with maximum degradation of 81.9% at 1 μM in MKN-45 cells. PRO-6E inhibits tumor growth in vivo and in vitro. PRO-6E induces cell apoptosis and induces cell arrest (Sturcture Note:(Blue: Cereblon ligand , Black: linker；Pink: ALK/c-Met inhibitor Crizotinib ).
PRO-6E (0.03-10 μM; 48 h) inhibits the cell growth in MKN-45, SNU-638 cells[1].PRO‐6 E (1 μM; over 24 h) facilitates MET degradation in MKN-45 cells[1].PRO‐6 E (0.1-1 μM; 48 h) increase in the percentage of G2/M phase cells and decrease in the percentage of S phase cells in MKN-45 cells[1].
PRO-6E (oral gavage; 30 mg/kg/day for 15 days) inhibits tumor growth in MKN‐45 cell‐derived xenograft tumor model[1].
References:
[1]. Chen JJ, et al. Crizotinib-based proteolysis targeting chimera suppresses gastric cancer by promoting MET degradation. Cancer Sci. 2023;114(5):1958-1971.