A BMI1 inhibitor
PTC-596 is an inhibitor of B cell-specific Moloney murine leukemia virus integration site 1 (BMI1), which is a member of the polycomb repressive complex 1 (PRC1) that has a role in gene silencing.1,2 It inhibits proliferation of MOLM-13 acute myeloid leukemia (AML) and Rec-1 mantle cell lymphoma (MCL) cancer cells (IC50s = 22.4 and 136 nM, respectively). It also induces BMI1 degradation in, and apoptosis of, the same cells. PTC-596 reduces microtubule polymerization and induces cell cycle arrest at the G2/M phase in MM.1S multiple myeloma cells.3 It decreases the number of side population cells, a unique cell population with stem-like characteristics, in Rec-1 cells (IC50 = 138 nM).2 PTC-596 (5 mg/kg, p.o.) increases survival in a MOLM-13 mouse xenograft model.1
1.Nishida, Y., Maeda, A., Kim, M.J., et al.The novel BMI-1 inhibitor PTC596 downregulates MCL-1 and induces p53-independent mitochondrial apoptosis in acute myeloid leukemia progenitor cellsBlood Cancer J.7(2)e527(2017) 2.Maeda, A., Nishida, Y., Weetall, M., et al.Targeting of BMI-1 expression by the novel small molecule PTC596 in mantle cell lymphomaOncotarget.9(47)28547-28560(2018) 3.Nagai, Y., Mimura, N., Rizq, O., et al.The combination of the tubulin binding small molecule PTC596 and proteasome inhibitors suppresses the growth of myeloma cellsSci. Rep.11(1)2074(2021)
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