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|Ref Type||Journal Article|
|Authors||Maes T, Mascaró C, Tirapu I, Estiarte A, Ciceri F, Lunardi S, Guibourt N, Perdones A, Lufino MMP, Somervaille TCP, Wiseman DH, Duy C, Melnick A, Willekens C, Ortega A, Martinell M, Valls N, Kurz G, Fyfe M, Castro-Palomino JC, Buesa C|
|Title||ORY-1001, a Potent and Selective Covalent KDM1A Inhibitor, for the Treatment of Acute Leukemia.|
|Date||2018 Mar 12|
|Abstract Text||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.|
|Molecular Profile||Treatment Approach|
|Gene Name||Source||Synonyms||Protein Domains||Gene Description||Gene Role|
|Drug Name||Trade Name||Synonyms||Drug Classes||Drug Description|
|ORY-1001||RO7051790|RO 7051790|RG6016|RG 6016|ORY 1001||KDM1A Inhibitor 12||ORY-1001 binds to and inhibits KDM1A (LSD1), leading to increased H3K4 dimethylation and potentially resulting in increased differentiation and decreased growth of tumor cells (PMID: 29502954).|
|Gene||Variant||Impact||Protein Effect||Variant Description||Associated with drug Resistance|
|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|Unknown unknown||acute myeloid leukemia||not applicable||ORY-1001||Preclinical - Cell line xenograft||Actionable||In a preclinical study, ORY-1001 decreased colony forming ability in several acute myeloid leukemia (AML) cell lines and primary AML samples in culture, and reduced tumor growth in AML cell line xenograft model (PMID: 29502954).||29502954|
|Unknown unknown||acute lymphoblastic leukemia||not applicable||ORY-1001||Preclinical - Pdx||Actionable||In a preclinical study, ORY-1001 reduced leukemic blast percentage and prolonged survival in a T-cell acute lymphoblastic leukemia patient-derived xenograft (PDX) model (PMID: 29502954).||29502954|