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 (C24IC50: 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。
| 生物活性 | MS177 is an effective and fast-actingEZH2degrader. MS177 is aPROTACthat consists of a CRBN ligand, linker, and a potent enzymaticEZH2 inhibitorC24 (C24IC50): 12 nM). MS177 effectively depletes both canonical EZH2–PRC2 and noncanonical EZH2–cMyc complexes. MS177 induces leukaemia cell growth inhibition,apoptosisand cell cycle progression arrest[1]. |
| IC50& Target[1] | |
体外研究
(In Vitro) | 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: | 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[1] | 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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体内研究
(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: | PDX animal model of MLL-r AML[1] | | Dosage: | 100 mg/kg | | Administration: | Intraperitoneal injection (i.p.), BID for 6 days. | | Result: | Inhibited tumor growth and prolonged survival. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | | Powder | -20°C | 3 years | | 4°C | 2 years | | In solvent | -80°C | 6 months | | -20°C | 1 month |
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| 溶解性数据 | In Vitro: DMSO : 125 mg/mL(136.76 mM;Need ultrasonic) 配制储备液 | 1 mM | 1.0941 mL | 5.4703 mL | 10.9407 mL | | 5 mM | 0.2188 mL | 1.0941 mL | 2.1881 mL | | 10 mM | 0.1094 mL | 0.5470 mL | 1.0941 mL |
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储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂： ——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；
以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶 1. 请依序添加每种溶剂： 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: 2.08 mg/mL (2.28 mM); Suspended solution; Need ultrasonic
此方案可获得 2.08 mg/mL (2.28 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。 以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。 *以上所有助溶剂都可在本网站选购。
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