MS4078

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

MS4078 是一种新型的 ALK PROTAC（降解剂），在 SU-DHL-1 淋巴瘤和 NCI-H2228 肺癌细胞中以浓度和时间依赖性方式有效降低致癌活性 ALK 融合蛋白的细胞水平 (DC50=11 nM) 。

MS4078 is a novel PROTAC (degrader) of ALK, potently decreases cellular levels of oncogenic active ALK fusion proteins in a concentration- and time-dependent manner in SU-DHL-1 lymphoma and NCI-H2228 lung cancer cells (DC50=11 nM); induces ALK protein degradation via cereblon and proteasome dependent mechanism, potently inhibits proliferation of SU-DHL-1?cells with IC50 of 33 nM.

MS4078 effectively inhibits cancer cell proliferation. MS4078 (10-3, 10-2.5, 10-2, 10-1.5, 10-1, 10-0.5, 1 μM; 3 days) concentration-dependently inhibits proliferation of SU-DHL-1?cells with an IC50?of?33±1??nM. In comparison with SU-DHL-1?cells, the proliferation of NCI-H2228?cells is less sensitive to MS4078(10-2, 10-1.5, 10-1, 10-0.5, 1, 100.5 μM; 3 days).MS4078 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, MS4078 reduces the NPM-ALK protein levels with impressive DC50 (50% degradation) value of?11±2?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, MS4078 reduces the EML4-ALK protein levels with similar DC50 value of?59?±?16?nM after 16-hour treatment.At the 100?nM concentration, NCI-H2228?cells reduces more than 90% of EML4-ALK protein levels. Cell Viability Assay 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, 100.5 μM for NCI-H2228?cells Incubation Time:3 days Result:Inhibited proliferation of SU-DHL-1?cells (IC50=33?±?1?nM). Less sensitive to the proliferation of NCI-H2228?cells than SU-DHL-1?cells.Western Blot Analysis 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 DC50 of ?11?±?2?nM in SU-DHL-1?cells. Reduced the EML4-ALK protein levels with similar DC50 of?59?±?16?nM in NCI-H2228?cells

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MS-4078 | MS 4078

PROTACs

PROTAC

PROTAC

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2229036-62-6

914.476

C45H52ClN9O8S

>98% (HPLC)

In Vitro:?DMSO : 50 mg/mL (54.68 mM)

O=C(NCCNC1=CC=CC(C(N2C(CC3)C(NC3=O)=O)=O)=C1C2=O)CN4CCC(C5=CC(OC(C)C)=C(NC6=NC=C(Cl)C(NC7=CC=CC=C7S(=O)(C(C)C)=O)=N6)C=C5C)CC4

2-(4-(4-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-5-isopropoxy-2-methylphenyl)piperidin-1-yl)-N-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethyl)acetamide

(-20℃)

With Ice Pack

≥ 2 years