Irreversible LSD1 Inhibitors: Application of Tranylcypromine and Its Derivatives in Cancer Treatment.

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