LSD1 inhibitor TAS1440

An orally available inhibitor of lysine-specific demethylase 1 (LSD1; KDM1A), with potential antineoplastic activity. Upon oral administration, LSD1 inhibitor TAS1440 specifically targets, binds to and inhibits LSD1, a demethylase that suppresses the expression of target genes by converting the di- and mono-methylated forms of lysine at position 4 of histone 3 (H3K4) to mono- and unmethylated H3K4, respectively. LSD1 inhibition enhances H3K4 methylation and increases the expression of tumor suppressor genes. This may lead to an inhibition of cell growth in LSD1-overexpressing tumor cells. In addition, LSD1 demethylates mono- or di-methylated H3K9 which increases gene expression of tumor promoting genes; inhibition of LSD1 promotes H3K9 methylation and decreases transcription of these genes. LSD1 is overexpressed in a number of tumor cell types. LSD1 acts on histone H3 as a transcription co-repressor through demethylation of lysine 4 (H3K4) or as a transcription co-activator through demethylation of lysine 9 (H3K9).