MS-177 is a PROTAC EZH2 degrader that promotes cholangiocarcinoma growth through the EZH2-mediated WNT7B/β-catenin pathway.MS-177 inhibits the growth of leukemia cells, induces apoptosis, and cell cycle arrest.MS-177 induces degradation of the classical EZH2-PRC2 and the non-classical EZH2-cMyc complexes and activates the immune-responsive genes in MM cells.

EZH2-PRC2:7 nM, MV4-11 cells:1.5 µM, MV4-11 cells:68% (Dmax), EOL-1 cells:82% (Dmax), EOL-1 cells:0.2 µM (DC50)

MS-177 inhibits the enzymatic activities of EZH2-PRC2 (IC50=7 nM). In EOL-1 and MV4;11 cells, MS-177 exhibited half-maximal degradation concentration (DC50) values of 0.2 µM and 1.5 µM, and maximum degradation (Dmax) values of 82% and 68%. [1]

Two doses of MS-177 (100 mg/kg intraperitoneally twice a day, 6 days per week; and 200 mg/kg intraperitoneally twice a day, 3 days per week) were well tolerated in mice and showed no significant toxicity. The antitumor effects of MS-177 were evaluated using a patient-derived xenograft (PDX) animal model of MLL-r AML, and both of the above MS-177 dosing regimens significantly inhibited AML growth in the PDX model, either established by seeding or subcutaneous inoculation, and prolonged survival, relative to controls. [1]