| Bioactivity | MS177 is an effective and fast-acting EZH2 degrader. MS177 is a PROTAC that consists of a CRBN ligand, linker, and a potent enzymatic EZH2 inhibitor C24 (C24 IC50): 12 nM). MS177 effectively depletes both canonical EZH2–PRC2 and noncanonical EZH2–cMyc complexes. MS177 induces leukaemia cell growth inhibition, apoptosis and cell cycle progression arrest[1]. | ||||||||||||
| Invitro | MS177 inhibits the enzymatic activities of EZH2-PRC2 (IC50: 7 nM)[1].MS177 (5 μM, 24 h) decreases H3K27me3 and increases H3K27activity in HeLa cells[1].MS177 (0.1-5 μM, 16 h) effectively degrades cellular EZH2-PRC2 and suppresses global H3K27me3 in EOL-1 cells[1].MS177 (0.1-5 μM, 16 h) induces Myc degradation in EOL-1 and MV4 cells[1].MS177 (4 days) shows antiproliferation effects in a panel of MLL-r leukaemia cells and samples from patients with AML, with IC50s below 2 μM[1].MS177 (0.5-2.5 μM, 24 h) decreases colony-forming capabilities in MV4;11 cells[1].MS177 (0.5-2.5 μM, 24 h) slows cell cycle progression and induces MOLM-13 cell apoptosis[1]. Cell Viability Assay[1] Cell Line: | ||||||||||||
| In Vivo | MS177 (100 mg/kg, i.p., BID for 6 days) represses tumor growth in PDX animal model of MLL-r AML, and in subcutaneously xenografted MLL-r leukaemia models[1].MS177 (50 mg/kg, i.p.) achieves intraplasma concentrations about 1 μM in male Swiss Albino mice[1].MS177 (100 mg/kg, i.p., BID for 6 days per week; and 200 mg/ kg, i.p. BID 3 days per week) is well tolerated and lacks apparent toxicity in mice[1]. Animal Model: | ||||||||||||
| Name | MS177 | ||||||||||||
| CAS | 2225938-86-1 | ||||||||||||
| Formula | C48H55N11O8 | ||||||||||||
| Molar Mass | 914.02 | ||||||||||||
| Appearance | Solid | ||||||||||||
| Transport | Room temperature in continental US; may vary elsewhere. | ||||||||||||
| Storage |
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| Reference | [1]. Wang J, et al. EZH2 noncanonically binds cMyc and p300 through a cryptic transactivation domain to mediate gene activation and promote oncogenesis. Nat Cell Biol. 2022 Mar;24(3):384-399. |