The heme enzyme myeloperoxidase (MPO) participates in innate immune defense mechanism through formation of microbicidal reactive oxidants. MPO-IN-28 is a the first potent, selective and mechanism-based irreversible MPO inhibitor with IC50 value of 44nM. MPO-IN-28 achieved residual MPO activity without H2O2 by 84%, residual MPO activity with H2O2 by 4%, residual MPO activity with Cl−+ H2O2 by 5% at 5μM and inhibited LDL oxidation with IC50 value of 0.09μM. It dose-dependently inhibited MPO inside neutrophils with IC50 value of 93.1μM. MPO-IN-28 possesses the characteristic of blood−brain barrier permeability, human intestinal absorption and cell permeability. It inhibited in vitro growth of normal human dermal fibroblast with IC50 value 17μM[2].
作用机制
MPO-IN-28 interacts with the active site of MPO and MPO uses hydrogen peroxide to oxidize MPO-IN-28 thereby irreversibly inactivating the enzyme.[2]
搜索
