Résumé : Myeloperoxidase (MPO) is a major player of the innate immune defense system of human neutrophils and catalyzes the prodn. of strong oxidizing and halogenating antimicrobial products. Because of its role in pathogenesis of many (inflammatory) diseases, there is great interest in the development of efficient and specific inhibitors. Here, using the X-ray structure of MPO, high-throughput mol. docking of 1350000 compds. was performed. From this virtual screening process, 81 were tested for inhibition of the chlorination activity of MPO, finally ending up with eight inhibiting candidates of different chem. structures. These were tested for inhibiting MPO-mediated low-d. lipoprotein oxidn. and for interacting with the relevant redox intermediates of MPO. The best inhibitors were bis-2,2'-[(dihydro-1,3(2H,4H)-pyrimidinediyl)bis(methylene)]phenol and 8-[(2-aminoethyl)amino]-3,7-dihydro-3-methyl-7-(3-phenoxypropyl)-1H-purine-2,6-dione. Both did not irreversibly inactivate the enzyme but efficiently trapped it in its compd. II state. We discuss the mechanism of inactivation as well as pros and cons of the performed selection process.