ORY-1001, a Potent and Selective Covalent KDM1A Inhibitor, for the Treatment of Acute Leukemia Academic Article uri icon


MeSH Major

  • Migraine Disorders
  • Pain Measurement
  • Pyrrolidines
  • Serotonin Receptor Agonists
  • Triazoles
  • Tryptamines


  • © 2018 Elsevier Inc. The 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. Maes et al. develop ORY-1001, a highly potent and selective inhibitor of KDM1A/LSD1. ORY-1001 induces differentiation of leukemic cells in cell lines, primary AML samples, and AML patients. ORY-1001 is able to decrease leukemic growth and prolong survival of mouse models of acute leukemia.

publication date

  • January 2018



  • Academic Article


Digital Object Identifier (DOI)

  • 10.1016/j.ccell.2018.02.002

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