ORY-1001 trans is a selective irreversible lysine (K)-specific demethylase 1A (KDM1A/LSD1) inhibitor. KDM1A/LSD1[1]
ORY-1001 trans is a KDM1A inhibitor that inactivate KDM1A by irreversible binding to the flavin adenine nucleotide (FAD) cofactor. ORY-1001 trans has very high selectivity for KDM1A over the MAO enzymes, high selectivity over KDM1B and unrivaled subnanomolar cellular activity in differentiation and colony formation assays on mixed lineage leukemia (MLL)-translocated acute myeloid leukemia (AML) cell lines. ORY-1001 provokes a time and dose-dependent induction of the Cd11b differentiation marker in MLL-AF9 cells, which interestingly preceeds changes in H3K4me2 levels. While MLL-translocated cells are especially sensitive, other acute leukemia (AL) cell lines also respond to ORY-1001 trans[1].
ORY-1001 trans reduces AML tumor growth in mice and rat xenografts and increases survival time in a disseminated model of T-ALL[1].
[1]. Maes T, et al. KDM1 histone lysine demethylases as targets for treatments of oncological and neurodegenerative disease. Epigenomics. 2015;7(4):609-26. doi: 10.2217/epi.15.9.