组蛋白去甲基化酶抑制剂;Histone Demethylase Inhibitors;;InformationIadademstat (ORY-1001) 2HCl ORY-1001 (RG-6016) 2HCl is an orally active and selective lysine-specific demethylase LSD1/KDM1A inhibitor with IC50 of <20 nM, with high selectivity against related FAD dependent aminoxidases. Phase 1.TargetsLSD1 20 nMIn vitroIn THP-1 (MLL-AF9) cells, ORY-1001 results in a time/dose dependent me2H3K4 accumulation at KDM1A target genes and concomitant induction of differentiation markers. ORY-1001 also induces apoptosis in THP-1 and inhibits proliferation and colony formation of MV(4;11) (MLL-AF4) cells.In vivoIn rodent MV(4;11) xenografts, ORY-1001 (<0.020mg/kg, p.o.) leads to significantly reduced tumor growth.