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
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.