MS1943 是一种首创的,具有口服生物活性的EZH2选择性降解剂,其IC50为 120 nM。MS1943 显著降低了许多三阴性乳腺癌和其他癌及非癌细胞系中的EZH2蛋白水平。MS1943 有效地阻止了多个三阴性乳腺癌和其他癌细胞系的增殖。
生物活性 | MS1943 is a first-in-class, orally bioavailableEZH2selective degrader, with anIC50of 120 nM. MS1943 significantly reducesEZH2protein levels in numerous triple-negative breastcancer(TNBC) and othercancerand noncancerous cell lines. MS1943 effectively blocks proliferation of multiple TNBC and othercancercell lines[1]. |
IC50& Target[1] | |
体外研究 (In Vitro) | MS1943 (0.625-5 μM; 3 days) inhibits cell growth with an GI50of 2.2 μM[1]. MS1943 (0.625-5 μM; 4 days) induces cell death in MDA-MB-468 cells. MS1943 effectively reduces EZH2 levels in BT549, HCC70 and MDA-MB-231 TNBC cells, as well as KARPAS-422 and SUDHL8 lymphoma cells and PNT2 non-cancerous prostate cells[1]. MS1943 (1.25-5.0 μM; 2 days) inhibits EZH2 and SUZ12 protein levels in a concentration- and timedependent manner, without affecting EED protein levels, whereas the H3K27me3 mark was also suppressed[1].
Cell Viability Assay[1] Cell Line: | MDA-MB-468 cells | Concentration: | 0.625, 1.25, 2.5, 5 μM | Incubation Time: | 3 days | Result: | Inhibits cell growth with an GI50of 2.2 μM. |
Western Blot Analysis[1] Cell Line: | MDA-MB-468 cells | Concentration: | 1.25, 2.5, 5.0 μM | Incubation Time: | 2 days | Result: | Reduced EZH2 protein levels in a concentration- and time-dependent manner. |
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体内研究 (In Vivo) | MS1943 (150 mg/kg body weight; i.p.; once daily for 36 days) suppresses tumor growth[1]. MS1943 induces apoptosis in the MDA-MB-468 xenograft model[1]. A single i.p. injection of MS1943 at 50 mg/kg body weight achieved a peak plasma concentration (Cmax) of 2.9 μM and resulted in plasma concentrations above its cellular IC50value for ~2h. A single 150 mg/kg body weight p.o. dose achieved Cmax of 1.1 μM, but plasma concentrations were below the cellular IC50value[1].
Animal Model: | Eight-week-old female BALB/c nude mice (MDA-MB-468 xenografts)[1] | Dosage: | 150 mg/kg body weight | Administration: | i.p.; once daily for 36 days | Result: | Suppresses tumor growth. |
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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(173.87 mM;Need ultrasonic) 配制储备液 1 mM | 1.3910 mL | 6.9548 mL | 13.9096 mL | 5 mM | 0.2782 mL | 1.3910 mL | 2.7819 mL | 10 mM | 0.1391 mL | 0.6955 mL | 1.3910 mL |
*请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液;一旦配成溶液,请分装保存,避免反复冻融造成的产品失效。 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: ≥ 6.25 mg/mL (8.69 mM); Clear solution
此方案可获得 ≥ 6.25 mg/mL (8.69 mM,饱和度未知) 的澄清溶液。 以 1 mL 工作液为例,取 100 μL 62.5 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。 2. 请依序添加每种溶剂: 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: ≥ 6.25 mg/mL (8.69 mM); Clear solution
此方案可获得 ≥ 6.25 mg/mL (8.69 mM,饱和度未知) 的澄清溶液。 以 1 mL 工作液为例,取 100 μL 62.5 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中,混合均匀。 3. 请依序添加每种溶剂: 10% DMSO 90%corn oil Solubility: ≥ 6.25 mg/mL (8.69 mM); Clear solution
此方案可获得 ≥ 6.25 mg/mL (8.69 mM,饱和度未知) 的澄清溶液,此方案不适用于实验周期在半个月以上的实验。 以 1 mL 工作液为例,取 100 μL 62.5 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中,混合均匀。 *以上所有助溶剂都可在本网站选购。
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