MS4077 is an anaplastic lymphoma kinase (ALK) PROTAC (degrader) based on Cereblon ligand, with a K_d of 37 nM for binding affinity to ALK^[1].

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^-2-10^0.5 μM; 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 DC₅₀ value 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].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

1134.73

C₅₅H₇₂ClN₉O₁₃S

2230077-10-6

Room temperature in continental US; may vary elsewhere.

-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)

DMSO : 110 mg/mL (96.94 mM; Need ultrasonic)

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°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light)。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

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。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

• 2.

  请依序添加每种溶剂： 10% DMSO    90% (20% SBE-β-CD in 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 μL 20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。

  将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明

• [1]. Zhang C, et al. Proteolysis Targeting Chimeras (PROTACs) of Anaplastic Lymphoma Kinase (ALK). Eur J Med Chem. 2018 May 10;151:304-314.