LTM-1

LTM-1 is a potent and highly selective small molecule inhibitor of Lysine-specific demethylase 1 (LSD1), currently in preclinical development for the treatment of acute myeloid leukemia (AML). Identified through an integrated screening strategy involving pharmacophore modeling and molecular docking, LTM-1 exhibits nanomolar inhibitory activity against LSD1 (IC50 = 2.11 nM) and demonstrates over 2370-fold selectivity over the related isoform LSD2. LSD1 is a flavin adenine dinucleotide (FAD)-dependent amine oxidase that acts as a key regulator of leukemia stem cell self-renewal by demethylating histone H3 lysine 4 (H3K4) and lysine 9 (H3K9). In preclinical models, LTM-1 has shown significant anti-proliferative effects against LSD1-addicted MV-4-11 leukemia cells and robust anti-tumor efficacy in xenograft mouse models without inducing significant systemic toxicity or impairment of liver and kidney functions.