MS177

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

MS177 是一种有效且快速起效的 EZH2 降解剂。MS177 是一种 PROTAC 分子，由 CRBN 配体、连接子和有效的酶促 EZH2 抑制剂 C24 组成 (C24 IC50: 12?nM)。MS177 可有效地消耗剥离 EZH2-PRC2 和非经典 EZH2-cMyc 复合物。MS177 抑制白血病细胞生长、诱导细胞凋亡和细胞周期阻滞。

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): 12nM). MS177 effectively depletes both canonical EZH2–PRC2 and noncanonical EZH2–cMyc complexes. MS177 induces leukaemia cell growth inhibition, apoptosis and cell cycle progression arrest.

MS177 (100mg/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.MS177 (50 mg/kg, i.p.) achieves intraplasma concentrations about 1 μM in male Swiss Albino mice.MS177 (100mg/kg, i.p., BID for 6 days per week; and 200mg/kg, i.p. BID 3 days per week) is well tolerated and lacks apparent toxicity in mice.Animal Model:PDX animal model of MLL-r AML Dosage:100 mg/kg Administration: Intraperitoneal injection (i.p.), BID for 6 days.Result:Inhibited tumor growth and prolonged survival.

MS177 inhibits the enzymatic activities of EZH2-PRC2 (IC50: 7nM).MS177 (5 μM, 24 h) decreases H3K27me3 and increases H3K27activity in HeLa cells.MS177 (0.1-5 μM, 16 h) effectively degrades cellular EZH2-PRC2 and suppresses global H3K27me3 in EOL-1 cells.MS177 (0.1-5 μM, 16 h) induces Myc degradation in EOL-1 and MV4 cells.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.MS177 (0.5-2.5 μM, 24 h) decreases colony-forming capabilities in MV4;11 cells.MS177 (0.5-2.5 μM, 24 h) slows cell cycle progression and induces MOLM-13 cell apoptosis.Cell Viability Assay Cell Line:AML cell line: MV4;11, MOML-13, RS4;11, KOPN-8 THP-1, EOL-1 (MLL-r cells) Control cell line: K562 (CML cells) Patient sample: AML cells Concentration:0-100 μM approximately Incubation Time:4 days Result:Inhibited cell proliferation with IC50s of 0.1-0.57 μM for MLL-r cells, 0.09-1.35 μM for Patient sample, >100 μM for K562 cell.Western Blot Analysis Cell Line:EOL-1 cell Concentration:0.1, 0.5, 1, 2.5, 5 μM Incubation Time:16 h Result:Depleted EZH2, EED and SUZ12 in a concentration-dependent manner and suppressed global H3K27me3.

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Others

Other Targets

EZH2

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2225938-86-1

914.02

C48H55N11O8

>98% (HPLC)

DMSO : 125 mg/mL (136.76 mM; ultraphonic; )

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(-20℃)

With Ice Pack

≥ 2 years