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Myeloid leukemia cell differentiation protein (MCL1)

In vitro studies identified a small molecule MCL1 inhibitor that could help treat leukemia. A competitive screen identified the small molecule MCL1 inhibitor molecule 1 (MIM1) as an MCL1 inhibitor. In MCL1-dependent acute lymphoblastic leukemia (ALL) cells, MIM1 induced caspase activity and decreased viability compared with vehicle. In ALL cells expressing both MCL1 and Bcl-xL, the B cell lymphoma 2 (BCL-2; BCL2) family inhibitor ABT-737 plus MIM1 led to synergistic cytotoxicity and decreased cell viability compared with either treatment alone. Ongoing work includes optimizing the potency of MIM1.
ABT-737 is a research reagent from Abbott Laboratories.

SciBX 5(39); doi:10.1038/scibx.2012.1029
Published online Oct. 4, 2012

Patent applications filed covering screening strategy and compounds identified by the screen, including MIM1; available for licensing

Cohen, N.A. et al. Chem. Biol.; published online Sept. 21, 2012;
Contact: Loren D. Walensky, Dana-Farber Cancer Institute, Boston, Mass.