{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T14:54:46Z","timestamp":1772895286251,"version":"3.50.1"},"reference-count":29,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2018,10,1]],"date-time":"2018-10-01T00:00:00Z","timestamp":1538352000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2018,10,1]],"date-time":"2018-10-01T00:00:00Z","timestamp":1538352000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,1,3]],"date-time":"2026-01-03T00:00:00Z","timestamp":1767398400000},"content-version":"am","delay-in-days":2651,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"content-domain":{"domain":["jpet.aspetjournals.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pharmacology and Experimental Therapeutics"],"published-print":{"date-parts":[[2018,10]]},"DOI":"10.1124\/jpet.118.248435","type":"journal-article","created":{"date-parts":[[2018,8,3]],"date-time":"2018-08-03T16:25:22Z","timestamp":1533313522000},"page":"147-154","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":12,"title":["Discovery of 1-((6-Aminopyridin-3-yl)Methyl)-3-(4-Bromophenyl)Urea as a Potent, Irreversible Myeloperoxidase Inhibitor"],"prefix":"10.1016","volume":"367","author":[{"given":"Martin L.","family":"Marro","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew W.","family":"Patterson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lac","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Deng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aimee","family":"Reynolds","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xianglin","family":"Ren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Axford","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anup","family":"Patnaik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Micah","family":"Hollis-Symynkywicz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nigel","family":"Casson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominique","family":"Custeau","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Ames","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sally","family":"Loi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lihe","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshiyuki","family":"Honda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jutta","family":"Blank","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tyler J.","family":"Harrison","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julien P.N.","family":"Papillon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lawrence G.","family":"Hamann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jovita","family":"Marcinkeviciene","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean B.","family":"Regard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1124\/jpet.118.248435_bib1","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1084\/jem.20021426","article-title":"Myeloperoxidase and plasminogen activator inhibitor 1 play a central role in ventricular remodeling after myocardial infarction","volume":"197","author":"Askari","year":"2003","journal-title":"J Exp Med"},{"key":"10.1124\/jpet.118.248435_bib2","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1172\/JCI8797","article-title":"Increased atherosclerosis in myeloperoxidase-deficient mice","volume":"107","author":"Brennan","year":"2001","journal-title":"J Clin Invest"},{"key":"10.1124\/jpet.118.248435_bib3","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.1194\/jlr.M600005-JLR200","article-title":"Transgenic mice express human MPO -463G\/A alleles at atherosclerotic lesions, developing hyperlipidemia and obesity in -463G males","volume":"47","author":"Castellani","year":"2006","journal-title":"J Lipid Res"},{"key":"10.1124\/jpet.118.248435_bib4","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1164\/rccm.201103-0468OC","article-title":"Late intervention with a myeloperoxidase inhibitor stops progression of experimental chronic obstructive pulmonary disease","volume":"185","author":"Churg","year":"2012","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1124\/jpet.118.248435_bib5","first-page":"1","article-title":"Evaluation of enzyme inhibitors in drug discovery. A guide for medicinal chemists and pharmacologists","volume":"46","author":"Copeland","year":"2005","journal-title":"Methods Biochem Anal"},{"key":"10.1124\/jpet.118.248435_bib6","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1124\/dmd.115.067868","article-title":"Pharmacokinetics and disposition of the thiouracil derivative PF-06282999, an orally bioavailable, irreversible inactivator of myeloperoxidase enzyme, across animals and humans","volume":"44","author":"Dong","year":"2016","journal-title":"Drug Metab Dispos"},{"key":"10.1124\/jpet.118.248435_bib7","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1189\/jlb.0109012","article-title":"Kinin B1 receptor activation turns on exocytosis of matrix metalloprotease-9 and myeloperoxidase in human neutrophils: involvement of mitogen-activated protein kinase family","volume":"86","author":"Ehrenfeld","year":"2009","journal-title":"J Leukoc Biol"},{"key":"10.1124\/jpet.118.248435_bib8","doi-asserted-by":"crossref","first-page":"2391","DOI":"10.1126\/science.1106830","article-title":"Myeloperoxidase, a leukocyte-derived vascular NO oxidase","volume":"296","author":"Eiserich","year":"2002","journal-title":"Science"},{"key":"10.1124\/jpet.118.248435_bib9","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/j.talanta.2009.07.052","article-title":"A new easy method for specific measurement of active myeloperoxidase in human biological fluids and tissue extracts","volume":"80","author":"Franck","year":"2009","journal-title":"Talanta"},{"key":"10.1124\/jpet.118.248435_bib10","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.1021\/bi201872j","article-title":"Deconstruction of activity-dependent covalent modification of heme in human neutrophil myeloperoxidase by multistage mass spectrometry (MS(4))","volume":"51","author":"Geoghegan","year":"2012","journal-title":"Biochemistry"},{"key":"10.1124\/jpet.118.248435_bib11","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1111\/j.1365-2362.2011.02601.x","article-title":"Plasma myeloperoxidase level and peripheral arterial disease","volume":"42","author":"Haslacher","year":"2012","journal-title":"Eur J Clin Invest"},{"key":"10.1124\/jpet.118.248435_bib12","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/j.nucmedbio.2015.02.001","article-title":"Development of rapid multistep carbon-11 radiosynthesis of the myeloperoxidase inhibitor AZD3241 to assess brain exposure by PET microdosing","volume":"42","author":"Johnstr\u00f6m","year":"2015","journal-title":"Nucl Med Biol"},{"key":"10.1124\/jpet.118.248435_bib13","doi-asserted-by":"crossref","first-page":"2687","DOI":"10.1093\/brain\/awv184","article-title":"Effect of the myeloperoxidase inhibitor AZD3241 on microglia: a PET study in Parkinson\u2019s disease","volume":"138","author":"Jucaite","year":"2015","journal-title":"Brain"},{"key":"10.1124\/jpet.118.248435_bib14","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/s12640-015-9547-7","article-title":"Failure of neuroprotection despite microglial suppression by delayed-start myeloperoxidase inhibition in a model of advanced multiple system atrophy: clinical implications","volume":"28","author":"Kaindlstorfer","year":"2015","journal-title":"Neurotox Res"},{"key":"10.1124\/jpet.118.248435_bib15","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1189\/jlb.1204697","article-title":"Myeloperoxidase: friend and foe","volume":"77","author":"Klebanoff","year":"2005","journal-title":"J Leukoc Biol"},{"key":"10.1124\/jpet.118.248435_bib16","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1159\/000041062","article-title":"Consequences of total and subtotal myeloperoxidase deficiency: risk or benefit?","volume":"104","author":"Kutter","year":"2000","journal-title":"Acta Haematol"},{"key":"10.1124\/jpet.118.248435_bib17","doi-asserted-by":"crossref","first-page":"47562","DOI":"10.1074\/jbc.M308428200","article-title":"Class B scavenger receptors CD36 and SR-BI are receptors for hypochlorite-modified low density lipoprotein","volume":"278","author":"Marsche","year":"2003","journal-title":"J Biol Chem"},{"key":"10.1124\/jpet.118.248435_bib18","doi-asserted-by":"crossref","first-page":"2798","DOI":"10.1161\/CIRCULATIONAHA.104.516278","article-title":"Expression of human myeloperoxidase by macrophages promotes atherosclerosis in mice","volume":"111","author":"McMillen","year":"2005","journal-title":"Circulation"},{"key":"10.1124\/jpet.118.248435_bib19","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1089\/ars.2012.4783","article-title":"Myeloperoxidase: a leukocyte-derived protagonist of inflammation and cardiovascular disease","volume":"18","author":"Nussbaum","year":"2013","journal-title":"Antioxid Redox Signal"},{"key":"10.1124\/jpet.118.248435_bib20","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1093\/eurheartj\/ehr193","article-title":"Myeloperoxidase deficiency preserves vasomotor function in humans","volume":"33","author":"Rudolph","year":"2012","journal-title":"Eur Heart J"},{"key":"10.1124\/jpet.118.248435_bib21","doi-asserted-by":"crossref","first-page":"8513","DOI":"10.1021\/acs.jmedchem.5b00963","article-title":"Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): a highly selective mechanism-based myeloperoxidase inhibitor for the treatment of cardiovascular diseases","volume":"58","author":"Ruggeri","year":"2015","journal-title":"J Med Chem"},{"key":"10.1124\/jpet.118.248435_bib22","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/0003-9861(62)90321-1","article-title":"Myeloperoxidase of the leucocyte of normal human blood. I. Content and localization","volume":"96","author":"Schultz","year":"1962","journal-title":"Arch Biochem Biophys"},{"key":"10.1124\/jpet.118.248435_bib23","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1021\/tx9003775","article-title":"Myeloperoxidase: an oxidative pathway for generating dysfunctional high-density lipoprotein","volume":"23","author":"Shao","year":"2010","journal-title":"Chem Res Toxicol"},{"key":"10.1124\/jpet.118.248435_bib24","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1007\/s12640-011-9294-3","article-title":"Myeloperoxidase inhibition ameliorates multiple system atrophy-like degeneration in a transgenic mouse model","volume":"21","author":"Stefanova","year":"2012","journal-title":"Neurotox Res"},{"key":"10.1124\/jpet.118.248435_bib25","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1161\/01.ATV.0000131784.50633.4f","article-title":"Hypochlorous acid, a macrophage product, induces endothelial apoptosis and tissue factor expression: involvement of myeloperoxidase-mediated oxidant in plaque erosion and thrombogenesis","volume":"24","author":"Sugiyama","year":"2004","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"10.1124\/jpet.118.248435_bib26","doi-asserted-by":"crossref","first-page":"37578","DOI":"10.1074\/jbc.M111.266981","article-title":"2-thioxanthines are mechanism-based inactivators of myeloperoxidase that block oxidative stress during inflammation","volume":"286","author":"Tid\u00e9n","year":"2011","journal-title":"J Biol Chem"},{"key":"10.1124\/jpet.118.248435_bib27","doi-asserted-by":"crossref","first-page":"31826","DOI":"10.1074\/jbc.M704894200","article-title":"Myeloperoxidase inactivates TIMP-1 by oxidizing its N-terminal cysteine residue: an oxidative mechanism for regulating proteolysis during inflammation","volume":"282","author":"Wang","year":"2007","journal-title":"J Biol Chem"},{"key":"10.1124\/jpet.118.248435_bib28","doi-asserted-by":"crossref","first-page":"H1469","DOI":"10.1152\/ajpheart.2001.281.4.H1469","article-title":"Endothelial dysfunction is induced by proinflammatory oxidant hypochlorous acid","volume":"281","author":"Zhang","year":"2001","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"10.1124\/jpet.118.248435_bib29","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1124\/jpet.114.221788","article-title":"PF-1355, a mechanism-based myeloperoxidase inhibitor, prevents immune complex vasculitis and anti-glomerular basement membrane glomerulonephritis","volume":"353","author":"Zheng","year":"2015","journal-title":"J Pharmacol Exp Ther"}],"container-title":["The Journal of Pharmacology and Experimental Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022356524266891?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022356524266891?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1124\/jpet.118.248435","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T21:46:02Z","timestamp":1750110362000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0022356524266891"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10]]},"references-count":29,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2018,10]]}},"alternative-id":["S0022356524266891"],"URL":"https:\/\/doi.org\/10.1124\/jpet.118.248435","relation":{},"ISSN":["0022-3565"],"issn-type":[{"value":"0022-3565","type":"print"}],"subject":[],"published":{"date-parts":[[2018,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Discovery of 1-((6-Aminopyridin-3-yl)Methyl)-3-(4-Bromophenyl)Urea as a Potent, Irreversible Myeloperoxidase Inhibitor","name":"articletitle","label":"Article Title"},{"value":"The Journal of Pharmacology and Experimental Therapeutics","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1124\/jpet.118.248435","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2018 by The American Society for Pharmacology and Experimental Therapeutics","name":"copyright","label":"Copyright"}]}}