MS4078 is a PROTAC targeting on ALK with DC50 value of 11nM, consist of ALK inhibitor ceritinib as a warhead linked to CRBN ligand Pomalidomide. Treatment with MS4078 led a degradation of both ALK fusion protein, including NPM-ALK of SU-DHL-1 cells and EML4-ALK of NCI-H2228 cells, as well as downregulation of ALK auto phosphorylation and down-steam STAT3 phosphorylation, in both cell lines in a dose-dependent manner at concentration ranging in 3-100nM for 16h and in a time-dependent manner at concentration of 30nM for SU-DHL-1 cells or 60nM for NCI-H2228 cells within 24h. MS4078 exhibited potent antiproliferation against SU-DHL-1 cells with IC50 value of 33nM post 3 days. MS4078 is available in mice through intraperitoneal administration with highest plasma concentration 3,000nM achieved at 2 h at dose of 50mg/kg. MS4748 and MS4740 work as the negative controls for MS4078[1].
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