Syntheses of LSD1/HDAC Inhibitors with Demonstrated Efficacy against Colorectal Cancer: In Vitro and In Vivo Studies Including Patient-Derived Organoids

Precedential evidence ascertaining the overexpression of LSD1 and HDACs in colorectal cancer spurred us to design a series of dual LSD1-HDAC inhibitors. Capitalizing on the modular nature of the three-component HDAC inhibitory model, tranylcypromine as a surface recognition motif was appended to zinc-binding motifs via diverse linkers. A compendium of hydroxamic acids was generated and evaluated for