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

Overview

abstract

  • 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.

publication date

  • March 1, 2018

Research

keywords

  • Cell Differentiation
  • Histone Demethylases
  • Leukemia, Myeloid, Acute

Identity

Scopus Document Identifier

  • 85042349039

Digital Object Identifier (DOI)

  • 10.1016/j.ccell.2018.02.002

PubMed ID

  • 29502954

Additional Document Info

volume

  • 33

issue

  • 3