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So far, compounds that have been developed as inhibitors of <jats:styled-content style=\"fixed-case\">NPP<\/jats:styled-content>1 lack potency and specificity. Quinazoline\u20104\u2010piperidine sulfamides (<jats:styled-content style=\"fixed-case\">QPS<\/jats:styled-content>) have been described as potent inhibitors of <jats:styled-content style=\"fixed-case\">NPP<\/jats:styled-content>1. However, their mode of inhibition as well as their selectivity and capacity to modify biological processes have not been investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>In the present series of experiments, we have evaluated the efficacy of two derivatives, <jats:styled-content style=\"fixed-case\">QPS<\/jats:styled-content>1\u20102, in inhibiting human <jats:styled-content style=\"fixed-case\">NPP<\/jats:styled-content>1, and we have evaluated the effect of the most potent derivative (<jats:styled-content style=\"fixed-case\">QPS<\/jats:styled-content>1) on other ectonucleotidases as well as on the ability of this compound to prevent phosphate\u2010induced mineralization of human primary aortic valve interstitial cells (<jats:styled-content style=\"fixed-case\">VICs<\/jats:styled-content>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>The <jats:styled-content style=\"fixed-case\">QPS<\/jats:styled-content>1 derivative is a potent (K<jats:sub>i<\/jats:sub> 59.3 \u00b1 5.4\u2009nM) and selective non\u2010competitive inhibitor of human <jats:styled-content style=\"fixed-case\">NPP<\/jats:styled-content>1. Moreover, <jats:styled-content style=\"fixed-case\">QPS<\/jats:styled-content>1 also significantly inhibited the <jats:styled-content style=\"fixed-case\">K121Q NPP<\/jats:styled-content>1 gene variant (K<jats:sub>i<\/jats:sub> 59.2 \u00b1 14.5\u2009nM), which is prevalent in the general population. <jats:styled-content style=\"fixed-case\">QPS<\/jats:styled-content>1 did not significantly alter the activity of other nucleotide metabolizing ectoenzymes expressed at the cell surface, namely <jats:styled-content style=\"fixed-case\">NPP<\/jats:styled-content>3, <jats:styled-content style=\"fixed-case\">NTPD<\/jats:styled-content>ases (1\u20133), ecto\u20105\u2032\u2010nucleotidase and <jats:styled-content style=\"fixed-case\">ALP<\/jats:styled-content>. Importantly, <jats:styled-content style=\"fixed-case\">QPS<\/jats:styled-content>1 in the low micromolar range (\u226410\u2009\u03bcM) prevented phosphate\u2010induced mineralization of <jats:styled-content style=\"fixed-case\">VICs<\/jats:styled-content> and lowered the rise of osteogenic genes as expected for <jats:styled-content style=\"fixed-case\">NPP<\/jats:styled-content>1 inhibition.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>We have provided evidence that <jats:styled-content style=\"fixed-case\">QPS<\/jats:styled-content>1 is a potent and selective non\u2010competitive inhibitor of <jats:styled-content style=\"fixed-case\">NPP<\/jats:styled-content>1 and that it prevented pathological mineralization in a cellular model.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13204","type":"journal-article","created":{"date-parts":[[2015,5,29]],"date-time":"2015-05-29T18:25:18Z","timestamp":1432923918000},"page":"4189-4199","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Quinazoline\u20104\u2010piperidine sulfamides are specific inhibitors of human <scp>NPP<\/scp>1 and prevent pathological mineralization of valve interstitial cells"],"prefix":"10.1111","volume":"172","author":[{"given":"Elnur Elyar","family":"Shayhidin","sequence":"first","affiliation":[{"name":"Laboratoire d'\u00c9tudes Mol\u00e9culaires des Valvulopathies (LEMV) Groupe de Recherche en Valvulopathies (GRV) Quebec Heart and Lung Institute\/Research Center Department of Surgery Universit\u00e9 Laval  QC Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elsa","family":"Forcellini","sequence":"additional","affiliation":[{"name":"Canada Research Chair 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