6yt2

Publication Abstract from PubMed

Diphenylene iodonium (DPI) is known for its inhibitory activities against many flavin- and heme-dependent enzymes and is often used as an NADPH oxidase inhibitor. We probed the efficacy of DPI on two well-known drug targets, the human monoamine oxidases MAO A and B. UV-visible spectrophotometry and steady-state kinetics experiments demonstrate that DPI acts as a competitive MAO inhibitor with Ki values of 1.7 microM and 0.3 microM for MAO A and MAO B, respectively. Elucidation of the crystal structure of human MAO B bound to the inhibitor revealed that DPI binds deeply in the active-site cavity to establish multiple hydrophobic interactions with the surrounding side chains and the flavin. These data prove that DPI is a genuine MAO inhibitor and the inhibition mechanism does not involve a reaction with the reduced flavin. This binding and inhibitory activity against MAOs, two major ROS-producing enzymes, will have to be carefully considered when interpreting experiments that rely on DPI for target validation and chemical biology studies on ROS functions.

Diphenylene iodonium is a non-covalent MAO inhibitor: a biochemical and structural analysis.,Iacovino LG, Reis J, Mai A, Binda C, Mattevi A ChemMedChem. 2020 May 27. doi: 10.1002/cmdc.202000264. PMID:32459875^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.