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
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 IC 50 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). 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 DC 50 (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 DC 50 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. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cell Viability AssayCell 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, 10 0.5 μM for NCI-H2228 cells Incubation Time: 3 days Result: Inhibited proliferation of SU-DHL-1 cells (IC 50 =46 ± 4 nM). Less sensitive to the proliferation of NCI-H2228 cells than SU-DHL-1 cells. Western Blot AnalysisCell 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 DC 50 of 3 ± 1 nM in SU-DHL-1 cells. Reduced the EML4-ALK protein levels with similar DC 50 of 34 ± 9 nM in NCI-H2228 cells.
