TitleORY-1001, a Potent and Selective Covalent KDM1A Inhibitor, for the Treatment of Acute Leukemia.
Publication TypeJournal Article
Year of Publication2018
AuthorsMaes, Tamara, Mascaró Cristina, Tirapu Iñigo, Estiarte Angels, Ciceri Filippo, Lunardi Serena, Guibourt Nathalie, Perdones Alvaro, Lufino Michele M. P., Somervaille Tim C. P., Wiseman Dan H., Duy Cihangir, Melnick Ari, Willekens Christophe, Ortega Alberto, Martinell Marc, Valls Nuria, Kurz Guido, Fyfe Matthew, Castro-Palomino Julio Cesar, and Buesa Carlos
JournalCancer Cell
Date Published2018 Mar 12
KeywordsAnimals, Apoptosis, Cell Differentiation, Cell Line, Tumor, Disease Models, Animal, Histone Demethylases, Humans, Leukemia, Myeloid, Acute, Mice, Stem Cells

<p>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.</p>

Alternate JournalCancer Cell
PubMed ID29502954
Grant ListC5759/A20971 / / Cancer Research UK / United Kingdom