1799633-27-4

S63845 is an inhibitor of myeloid cell leukemia 1 (Mcl-1; K_i = 0.19 nM), a pro-survival protein that is overexpressed in many cancers. It induces cell death in multiple myeloma, leukemia, and lymphoma cell lines (IC₅₀s = <0.1-282 nM) via mitochondrial apoptosis. S63845 acts synergistically with trametinib (Item No. 16292), lapatinib (Item No. 11493), PLX4032 (Item No. 10618), and erlotinib (Item No. 10483) to reduce proliferation of SK-MEL-2, BT474, A2058, and PC9 cells, respectively. S63845 (6.25-25 mg/kg) reduces tumor volume in an MV4-11 acute myeloid leukemia mouse xenograft model in a dose-dependent manner.

S-63845 is used in killing senescent cells and treating senescence-associated diseases or disorders using a combination of a BCL inhibitor and an MCL-1 inhibitor.Potent and selective MCL1 inhibitor

MCL1: 0.19 nM (Kd)

[1] ANDRáS KOTSCHY. The MCL1 inhibitor S63845 is tolerable and effective in diverse cancer models[J]. Nature, 2016, 538 7626: 477-482. DOI: 10.1038/nature19830