Description
Lysine-specific demethylase 1 (LSD1) demethylates H3K4 and H3K9, resulting in transcriptional repression. It also controls the tumor suppressor activity of p53 by demethylating a specific p53 lysine residue (LYS
370). ORY-1001 is an orally available, selective inhibitor of LSD1 (IC
50 < 20 nM). It targets acute myeloid leukemia (AML) stem cells and significantly reduces tumor cell load while increasing survival time in mouse models of AML. ORY-1001 is in clinical trials for cancer treatment.
Uses
ORY-1001 is a potent LSD1 inhibitor.
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].
