ORY-1001 trans and cis isomers

ORY-1001 (RG-6016) is a highly potent, selective inhibitor of lysine-specific demethylase KDM1A (LSD1) with IC50 of 18 nM, displays high selectivity for KDM1A over other FAD-containing monoamine oxidases; exhibits low nanomolar cellular activity (EC50 < 1 nM) in the THP1 differentiation assay and induces the CD11b marker within 6 hr of treatment in FACS based differentiation assay in THP1 cell line; induces H3K4me2 accumulation on KDM1A target genes, blast differentiation, and reduction of leukemic stem cell capacity in AML; exhibits potent synergy with standard-of-care drugs and selective epigenetic inhibitors, reduces growth of AML xenograft models.Blood Cancer Phase 2 Clinical.