Bomedmestat (USAN; IUPAC name N-[(2S)-5-[[(1R,2S)-2-(4-fluorophenyl)cyclopropyl]amino]-1-(4-methylpiperazin-1-yl)-1-oxopentan-2-yl]-4-(triazol-1-yl)benzamide) is an investigational drug under development by Imago BioSciences for the treatment of myeloproliferative neoplasms including essential thrombocythemia, polycythemia vera, myelofibrosis[1] and small-cell lung cancer.

The first step in the catalytic reaction of LSD1 involves the abstraction of hydride from the target methyl of the H3K4 sidechain N-methyl by the oxidized state of a non-covalently bound FAD prosthetic group at the LSD1 active site to give a stabilized methylene iminium ion.

The overall reaction stoichiometry thus involves the conversion of an N-methyl group by water and oxygen to give molecules of formaldehyde, hydrogen peroxide, and the product N-H terminus.

LSD1 cannot demethylate H3K4 trimethyl (N-tri-methyl-lysine) because the initial iminium species cannot be formed owing to a lack of an available lone electron pair at the N-center, essential for formation of the requisite stabilizing pi-system.

In the irreversible inhibition of LSD1 by bomedemstat, the initial hydride abstraction event by the oxidized FAD center targets the free cyclopropyl methylene generating an unstable carbo-cation which rapidly rearranges to form an unbound but stabilized conjugated iminium cation intermediate.