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ORY-1001/RG6016 effect on leukemia cell lines

ABSTRACT: The lysine-specific demethylase LSD1/KDM1A is a key regulator of stem cell potential in acute myeloid leukemia (AML). Inhibition of its expression or catalytic activity overcomes the differentiation block and reduces colony formation potential. We have developed ORY-1001 as highly potent and selective inhibitor of KDM1A. Treatment of AML cell lines with ORY-1001 induces accumulation of H3K4me2 marks at KDM1A target genes, compromises leukemic stem cell capacity, and provokes blast differentiation. ORY-1001 exhibits potent synergy with standard of care drugs and with inhibitors of other epigenetic targets; reduces tumor growth and extends survival in mouse xenograft models of acute leukemia. To develop tools for use in clinical trials, we selected a panel of surrogate biomarkers for pharmacodynamic analysis based on expression changes in a panel of 24 leukemia cell lines. ORY-1001/RG6016 was the first selective KDM1A inhibitor to enter the clinic and is currently being evaluated in leukemia and solid tumor clinical trials.

ORGANISM(S): Homo sapiens

PROVIDER: GSE94567 | GEO | 2018/08/19

REPOSITORIES: GEO

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