molecules of the month

“Compound 34” is a mechanism-based inhibitor of lysine-specific demethylase LSD1 (aka KDM1A). LSD1 has an FAD co-factor which is covalently modified by the cyclopropylamine in compound 34 likely through an electron-transfer mechanism (as for tranylcypromine and MAOs). Interestingly, the 4,4-spiro amine provided an improvement to in vitro microsomal stability over the corresponding piperidine analog without a significant change in cLogD. The compound demonstrated activity in a xenograft model at doses as low as 0.5 mg/kg QD.