ORY-1001, a potent and selective covalent KDM1A inhibitor, for the treatment of acute leukemia.
Somervaille, Tim C P
Wiseman, Daniel H
AffiliationOryzon Genomics, S.A. Carrer Sant Ferran 74, 08940 Cornella de Llobregat, Spain
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AbstractThe lysine-specific demethylase KDM1A is a key regulator of stem cell potential in acute myeloid leukemia (AML). ORY-1001 is a highly potent and selective KDM1A inhibitor that induces H3K4me2 accumulation on KDM1A target genes, blast differentiation, and reduction of leukemic stem cell capacity in AML. ORY-1001 exhibits potent synergy with standard-of-care drugs and selective epigenetic inhibitors, reduces growth of an AML xenograft model, and extends survival in a mouse PDX (patient-derived xenograft) model of T cell acute leukemia. Surrogate pharmacodynamic biomarkers developed based on expression changes in leukemia cell lines were translated to samples from patients treated with ORY-1001. ORY-1001 is a selective KDM1A inhibitor in clinical trials and is currently being evaluated in patients with leukemia and solid tumors.
CitationORY-1001, a potent and selective covalent KDM1A inhibitor, for the treatment of acute leukemia. 2018, 33(3): 495-511.e12 Cancer Cell