MS4077 是基于Cereblon配体的间变性淋巴瘤激酶 (ALK)PROTAC(降解物)，结合 ALK,Kd为 37 nM。
| 生物活性 | MS4077 is ananaplastic lymphoma kinase(ALK)PROTAC(degrader) based onCereblonligand, with aKdof 37 nM for binding affinity to ALK[1]. |
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体外研究
(In Vitro) | MS4077 effectively inhibits cancer cell proliferation. MS4077 (10-3-1 μM; 3 days) concentration-dependently inhibits proliferation of SU-DHL-1 cells with an IC50 of 46 ± 4 nM. In comparison with SU-DHL-1 cells, the proliferation of NCI-H2228 cells is less sensitive to MS4077(10-2-100.5μM; 3 days)[1].
MS4077 potently reduces the ALK fusion protein levels and inhibits the ALK auto-phosphorylation and down-steam STAT3 phosphorylation in both SU-DHL-1 and NCI-H2228 cells in a concentration-dependent manner. In SU-DHL-1 cells, MS4077 reduces the NPM-ALK protein levels with impressive DC50(50% degradation) value of 3±1 nM after 16-hour treatment. Over 90% of inhibition of both ALK Y1507 and STAT3 Y705 phosphorylation is achieved at the 100 nM concentration. In NCI-H2228 cells, MS4077 reduces the EML4-ALK protein levels with similar DC50value of 34±9 nM after 16-hour treatment. At the 100 nM concentration, NCI-H2228 cells reduces more than 90% of EML4-ALK protein levels[1].
Cell Viability Assay[1] | Cell Line: | SU-DHL-1 and NCI-H2228 cells | | Concentration: | 10-3, 10-2.5, 10-2,10-1.5, 10-1, 10-0.5, and 1 μM for SU-DHL-1 cells; 10-2, 10-1.5, 10-1, 10-0.5, 1, 100.5μM for NCI-H2228 cells | | Incubation Time: | 3 days | | Result: | Inhibited proliferation of SU-DHL-1 cells (IC50=46 ± 4 nM). Less sensitive to the proliferation of NCI-H2228 cells than SU-DHL-1 cells. |
Western Blot Analysis[1] | Cell Line: | SU-DHL-1 and NCI-H2228 cells | | Concentration: | 1, 3, 10, 30, and 100 μM for SU-DHL-1 cells; 3, 10, 30, 60, and 100 μM for NCI-H2228 cells | | Incubation Time: | 16 hours | | Result: | Reduced the NPM-ALK protein levels with impressive DC50of 3 ± 1 nM in SU-DHL-1 cells. Reduced the EML4-ALK protein levels with similar DC50of 34 ± 9 nM in NCI-H2228 cells. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | -20°C, sealed storage, away from moisture and light *In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light) |
| 溶解性数据 | In Vitro: DMSO : 110 mg/mL(96.94 mM;Need ultrasonic) 配制储备液 | 1 mM | 0.8813 mL | 4.4063 mL | 8.8127 mL | | 5 mM | 0.1763 mL | 0.8813 mL | 1.7625 mL | | 10 mM | 0.0881 mL | 0.4406 mL | 0.8813 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 (sealed storage, away from moisture and light)。-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 mg/mL (5.29 mM); Suspended solution; Need ultrasonic
此方案可获得 6 mg/mL (5.29 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 60.0 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 mg/mL (5.29 mM); Clear solution
此方案可获得 ≥ 6 mg/mL (5.29 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 60.0 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。 *以上所有助溶剂都可在本网站选购。
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