MS4077

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]. IC50 & Target:Kd: 37±4nM (ALK)^[1]
PROTAC^[1] 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^-2-10^0.5 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].