| Literature DB >> 29502954 |
Tamara Maes1, Cristina Mascaró2, Iñigo Tirapu2, Angels Estiarte2, Filippo Ciceri2, Serena Lunardi2, Nathalie Guibourt2, Alvaro Perdones2, Michele M P Lufino2, Tim C P Somervaille3, Dan H Wiseman3, Cihangir Duy4, Ari Melnick5, Christophe Willekens6, Alberto Ortega2, Marc Martinell2, Nuria Valls2, Guido Kurz2, Matthew Fyfe2, Julio Cesar Castro-Palomino2, Carlos Buesa2.
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.Entities:
Keywords: KDM1A; LSD1; ORY-1001; acute myeloid leukemia; differentiation; epigenetic; histone methylation
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Year: 2018 PMID： 29502954 DOI： 10.1016/j.ccell.2018.02.002
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743