Synthesis of Carboxamides Tranylcypromine Analogues as LSD1 (KDM1A) Inhibitors for AML

21 February 2020, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

Lysine-specific demethylase 1 (LSD1/KDM1A) oxidatively removes methyl groups from histone proteins and its aberrant activity has been correlated with cancers including acute myeloid leukemia (AML). We report a novel series of tranylcypromine analogues containing a carboxamide at the 4-position of the aryl ring and novel carbamates. These compounds were potent submicromolar LSD1 inhibitors in enzyme assays and were anti-proliferative against a panel of AML cell lines. LSD1 target engagement in cells was demonstrated through the effects on H3K4me2 protein expression, CD86, CD11b and CD14 levels

Keywords

KDM1A, LSD1, AML

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