MS4077 是基于 Cereblon 配体的间变性淋巴瘤激酶 (ALK) PROTAC (降解物)，结合 ALK, K_d 为 37 nM。

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.

Solid

ALK Cereblon

MS4077 effectively inhibits cancer cell proliferation. MS4077 (10-1 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(10-10 μM; 3 days).
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

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)

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

In Vitro: DMSO : 110 mg/mL (96.94 mM; Need ultrasonic)配制储备液