Fig. 6
From: The timeline of epigenetic drug discovery: from reality to dreams
The mechanism of action of tranylcypromine and tranylcypromine analogues in clinical trials as LSD1 inhibitors. The monoamine oxidase inhibitor tranylcypromine (compound 37) binds as a suicide substrate in the MAO or LSD active site and then undergoes strain-induced ring opening to give a reactive radical cation (compound 38). This reactive intermediate covalently adds to the FAD cofactor thereby irreversibly inhibiting the enzyme. Tranylcypromine analogues are being developed to improve inhibition, including ORY-1001 (compound 39), GSK2879552 (compound 40), and 4SC-202 (compound 41)