Due to the increasing costs and time consuming for new
drug discovery, a large number of
pharmaceutical firms have chosen to modify the existing
drug molecules for repositioning candidates with new or improved properties, especially those with severe adverse effects, thereby accelerating the
drug discovery process. Such strategy has witnessed its success with several examples reported. As the first identified
histone lysine specific demethylase,
lysine specific demethylase 1 (LSD1) is classified as a member of
monoamine oxidase (
MAO) superfamily, and specifically removes mono- and dimethylated
histone 3
lysine 4 (H3K4) and H3
lysine 9 (H3K9). It has been reported that LSD1 and its downstream targets are involved in
cancer cell growth and
metastasis. Meanwhile, it is overexpressed in a variety of
tumor cells. Inactivating LSD1 specifically inhibits
tumor progression and
metastasis. Hence, LSD1 inhibition may represent a new and promising direction in anti-
cancer drug discovery. Based on the structure and cofactor of LSD1, some clinical applied
MAO inhibitors have been identified as LSD1 inactivators. Among them,
tranylcypromine presented the most potency against LSD1 and its derivatives were further developed by medicinal chemists in order to develop potent and selective LSD1 inhibitors. Currently, a number of
tranylcypromine based LSD1 inhibitors have been developed and two of them, ORY-1001 and
GSK2879552, are in clinical trials for
cancer treatment. This review highlights recent advances in the repurposing of
tranylcypromine and its derivatives as irreversible LSD1 inhibitors for
cancer treatment, which are conventionally used for the treatment of depression.