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ORY-1001, a potent and selective covalent KDM1A inhibitor, for the treatment of acute leukemia.
Maes, T Mascaró, C Tirapu, I Estiarte, A Ciceri, F Lunardi, S Guibourt, N Perdones, A Lufino, M Somervaille, Tim C P
Maes, T
Mascaró, C
Tirapu, I
Estiarte, A
Ciceri, F
Lunardi, S
Guibourt, N
Perdones, A
Lufino, M
Somervaille, Tim C P
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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.
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Date
2018-03-12
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Article
Citation
ORY-1001, a potent and selective covalent KDM1A inhibitor, for the treatment of acute leukemia. 2018, 33(3): 495-511.e12 Cancer Cell