MS4078 

MS4078 is an anaplastic lymphoma kinase (ALK) PROTAC (degrader) based on Cereblon ligand, with a K_d of 19 nM for binding affinity to ALK^[1].

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, 10^0.5 μM; 3 days)^[1].
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^[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

914.47

Solid

C₄₅H₅₂ClN₉O₈S

2229036-62-6

CC(C)S(C1=C(NC2=NC(NC3=C(OC(C)C)C=C(C4CCN(CC(NCCNC5=C(C(N(C6C(NC(CC6)=O)=O)C7=O)=O)C7=CC=C5)=O)CC4)C(C)=C3)=NC=C2Cl)C=CC=C1)(=O)=O

Room temperature in continental US; may vary elsewhere.

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