S63845 is a selective myeloid leukemia 1(MCL1) inhibitor that binds to human MCL1 with a Kd of 0.19 nM.

HH cells:22 nM (EC50), MDA-MB-468 cells:141.2 ± 24.7 nM (EC50), HCC1143 cells:3.1 ± 0.5 μM (EC50), HuT78 cells:110 nM (EC50), MCL1:0.19 nM (Kd)

METHODS: HCT-116 cells were treated with S63845 (0.001-10 μM), and the levels of MCL1 and BCL-XL proteins in the cells were analyzed by Western blot.
RESULTS S63845 effectively increased the level of MCL1 protein in the HCT-116 colon cancer cell line, but had no effect on the level of BCL-XL protein. The increase in MCL1 protein level was not accompanied by an increase in MCL1 mRNA level, but was associated with a prolonged protein half-life. [1]

METHODS: S63845 (6.25, 12.5, 25 mg/kg, intravenous injection) was used to treat immunocompromised mice bearing human multiple myeloma (H929 and AMO1) xenografts, and its antitumor activity was observed.
RESULTS S63845 showed dose-dependent antitumor activity; the maximum tumor growth inhibition (TGImax) was 114% in the AMO1 model and 103% in the H929 model. [1]