Tranylcypromine-based LSD1 inhibitors: structure-activity relationships, antiproliferative effects in leukemia, and gene target modulation
Abstract: LSD1 is a lysine demethylase highly involved in initiation and development of cancer. To design highly effective covalent inhibitors, a strategy is to fill its large catalytic cleft by designing tranylcypromine (TCP) analogs decorated with long, hindered substituents. We prepared three series of TCP analogs, carrying aroyl- and arylacetylamino (1 a–h), Z-amino acylamino (2 a–o), or double-substituted benzamide (3 a–n) residues at the C4 or C3 position of the phenyl ring.