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In this study, <jats:italic>N<\/jats:italic><jats:sup>5<\/jats:sup>\u2010(1\u2010imino\u20102\u2010chloroethyl)\u2010<jats:sc>L<\/jats:sc>\u2010ornithine (Cl\u2010NIO) is shown to be a potent time\u2010 and concentration\u2010dependent inhibitor of purified human DDAH\u20101 (<jats:italic>K<\/jats:italic><jats:sub>I<\/jats:sub>=1.3\u00b10.6\u2005\u03bc<jats:sc>M<\/jats:sc>; <jats:italic>k<\/jats:italic><jats:sub>inact<\/jats:sub>=0.34\u00b10.07\u2005min<jats:sup>\u22121<\/jats:sup>), with &gt;500\u2010fold selectivity against two arginine\u2010handling enzymes in the same pathway. An activity probe is used to measure the \u201cin cell\u201d IC<jats:sub>50<\/jats:sub> value (6.6\u00b10.2\u2005\u03bc<jats:sc>M<\/jats:sc>) for Cl\u2010NIO inhibition of DDAH\u20101 artificially expressed within cultured HEK293T cells. A screen of diverse melanoma cell lines reveals that a striking 50\/64 (78\u2009%) of melanoma lines tested showed increased levels of DDAH\u20101 relative to normal melanocyte control lines. Treatment of the melanoma A375 cell line with Cl\u2010NIO shows a subsequent decrease in cellular nitric oxide production. Cl\u2010NIO is a promising tool for the study of methylarginine\u2010mediated nitric oxide control and a potential therapeutic lead compound for other indications with elevated nitric oxide production, such as septic shock and idiopathic pulmonary fibrosis.<\/jats:p>","DOI":"10.1002\/cmdc.201300557","type":"journal-article","created":{"date-parts":[[2014,2,26]],"date-time":"2014-02-26T15:58:21Z","timestamp":1393430301000},"page":"792-797","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Developing an Irreversible Inhibitor of Human DDAH\u20101, an Enzyme Upregulated in Melanoma"],"prefix":"10.1002","volume":"9","author":[{"given":"Yun","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shougang","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Abdul M.","family":"Gabisi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joyce A. 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