CAS NO: | 1431326-61-2 |
规格: | 98% |
分子量: | 303.27 |
包装 | 价格(元) |
5mg | 电议 |
25mg | 电议 |
Background:
IC50:<20nM
Lysine (K)-specific demethylase 1A (KDM1A, aka LSD1) is a key regulator of leukemia stem cell (LSC) potential and is required for MLL-AF9 oncogenic transformation. Inhibition of KDM1A expression or activity overcomes the differentiation block in AML. ORY-1001 is a selective inhibitor of KDM1A.
In vitro: ORY-1001 is an enantiomerically pure KDM1A inhibitor with high selectivity against related FAD dependent aminoxidases. ORY-1001 does not inhibit non-related histone modifiers, and is clean in a CEREP diversity panel. Treatment of THP-1 cells with ORY-1001, results in a time/dose dependent me2H3K4 accumulation at KDM1A target genes and concomitant induction of differentiation markers [1].
In vivo: Daily oral administration of doses< 0.020 mg/kg leads to significantly reduced tumor growth in rodent xenografts. In vivo studies have shown that ORY-1001 presents excellent oral bioavailability, target exposure and activity in vivo [1].
Clinical trial: Oryzon Genomics announced the dosing of the first patient in the extension cohort (Part 2) of its ORY-1001 Phase I clinical trial. The trial will take place in 10 centers in Spain, UK and France.
Reference:
[1] Tamara Maes, I?igo Tirapu, Cristina Mascaró, Alberto Ortega, Angels Estiarte, Nuria Valls, Julio Castro-Palomino, Carlos Buesa Arjol, Guido Kurz; Oryzon Genomics, S. A., Cornella de Llobregat. Preclinical characterization of a potent and selective inhibitor of the histone demethylase KDM1A for MLL leukemia. J Clin Oncol 31, 2013 (suppl; abstr e13543).
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