Biological Activity
| Target | Value |
LSD1
() | 2.1 nM |
Biological Activity
T-3775440 hydrochloride is an irreversible LSD1 inhibitor. It is highly selective for LSD1 relative to other monoamine oxidases with IC50 of 2.1 nM.
in vitro
T-3775440 hydrochloride enhances the transdifferentiation of erythrocytes/megakaryocytes to granule-like monocytes. It disrupts the interaction of LSD1 and GFI1B. AEL (TF-1a, HEL92.1.7) cells and AMKL (CMK11-5, M07e) cells were treated with T-3775440 for 48 hours, which induced cell cycle arrest and apoptosis. In TF-1a and CMK11-5 cells, treatment with T-3775440 increased cells in G1 and sub-G1 phases.
in vivo
T-3775440 inhibits tumor growth in a mouse xenograft model of AML. In mice T-3775440 hydrochloride caused a transient decrease in platelets followed by a large rebound. After a single dose, it had no apparent effect on red blood cell counts. T-3775440 hydrochloride also exerted antitumor activity in AEL (HEL 92.1.7) model and AMKL (CMK11-5) model.
