ORY-1001，一种强效和选择性的 Covalent KDM1A 抑制剂，用于治疗急性白血病。
ORY-1001, a Potent and Selective Covalent KDM1A Inhibitor, for the Treatment of Acute Leukemia.
机构信息
Oryzon Genomics, S.A. Carrer Sant Ferran 74, 08940 Cornellà de Llobregat, Spain.
Oryzon Genomics, S.A. Carrer Sant Ferran 74, 08940 Cornellà de Llobregat, Spain.
出版信息
Cancer Cell. 2018 Mar 12;33(3):495-511.e12. doi: 10.1016/j.ccell.2018.02.002. Epub 2018 Mar 1.
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.
赖氨酸特异性去甲基酶 KDM1A 是急性髓细胞白血病（AML）中干细胞潜能的关键调节因子。ORY-1001 是一种高效且选择性的 KDM1A 抑制剂，可诱导 KDM1A 靶基因上的 H3K4me2 积累、分化为原始细胞、降低 AML 中的白血病干细胞能力。ORY-1001 与标准治疗药物和选择性表观遗传抑制剂具有强大的协同作用，可减少 AML 异种移植模型中的肿瘤生长，并延长 T 细胞急性白血病患者 PDX（患者来源的异种移植）模型中的存活时间。基于白血病细胞系表达变化开发的替代药效动力学生物标志物已转化为接受 ORY-1001 治疗的患者的样本。ORY-1001 是一种在临床试验中具有选择性的 KDM1A 抑制剂，目前正在接受白血病和实体瘤患者的评估。
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