We show that the FAD-drug adduct undergoes a Grob fragmentation to create formyl-FAD. We then show how mutations in LSD1 can promote fragmentation & drug resistance in leukemia cells, expanding our views on resistance mechanisms. An awesome trans-Atlantic team effort!
www.nature.com/articles/s41...
nature.com
Covalent adduct Grob fragmentation underlies LSD1 demethylase-specific inhibitor mechanism of action and resistance - Nature Communications
Next generation precision lysine-specific histone demethylase 1A (LSD1) covalent inhibitors which selectively block LSD1 enzyme activity by forming a compact N-formyl-FAD adduct have been developed, b...