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Lysine-specific demethylase 1 (LSD1) is a protein lysine demethylase that specifically demethylates histone H3 lysine 4 (H3K4), resulting in transcriptional repression. SP2509 is a reversible inhibitor of LSD1 (IC50 = 13 nM). It has no effect on monoamine oxidases A and B. SP2509 attenuates the binding of LSD1 to CoREST, allowing increased methylation of H3K4 and driving increased expression of p21, p27, and CCAAT/enhancer binding protein alpha in cultured acute myeloid leukemia (AML) cells. It improves survival of mice with AML xenografts when given (25 mg/kg biweekly via intraperitoneal injection) for three weeks. Co-treatment of SP2509 with the pan-HDAC inhibitor panobinostat (Cay-13280) synergistically kills AML cells in vitro and improves survival of mice engrafted with AML cells.