Pharmacological inhibition of LSD1 for the treatment of MLL-rearranged leukemia.

ABSTRACT:

Background

Mixed lineage leukemia (MLL) gene translocations are found in ~75% infant and 10% adult acute leukemia, showing a poor prognosis. Lysine-specific demethylase 1 (LSD1) has recently been implicated to be a drug target for this subtype of leukemia. More studies using potent LSD1 inhibitors against MLL-rearranged leukemia are needed.

Methods

LSD1 inhibitors were examined for their biochemical and biological activities against LSD1 and MLL-rearranged leukemia as well as other cancer cells.

Results

Potent LSD1 inhibitors with biochemical IC50 values of 9.8-77 nM were found to strongly inhibit proliferation of MLL-rearranged leukemia cells with EC50 of 10-320 nM, while these compounds are generally non-cytotoxic to several other tumor cells. LSD1 inhibition increa

SUBMITTER: Feng Z 

PROVIDER: S-EPMC4789278 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature