An Overview on Screening Methods for Lysine Specific Demethylase 1 (LSD1) Inhibitors

Abstract

Background: In the past few years, great of attention has been paid to the identification and characterization of selective and potent inhibitors of the first identified histone demethylase LSD1, which may erase mono- and di-methylated histone 3 lysine 4 and 9. As the aberrant overexpression of LSD1 is involved in various pathological processes, especially cancer, obtaining selective and potent LSD1 inhibitors has emerged as a crucial issue in medicinal chemistry research.

Method: Until now, several LSD1 inhibitor screening models have been established, including enzyme coupled assay, LC-MS based assay, and FRET based assay. Nevertheless, due to some special instrument requirement and additional costs of LC-MS and FRET, the enzyme coupled assay is the most widely applied method for LSD1 inhibitor screening.

Result: We summarized and compared several reported in vitro LSD1 inhibitor screening models. Each of them has distinct advantages and disadvantages, and none of these methods is perfect. In order to exclude the false positive results, at least one additional method should be applied to screen LSD1 inhibitors.

Keywords: FRET; LC-MS; LSD1; enzyme coupled assay; inhibitor; screening model.