{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T08:01:28Z","timestamp":1777536088793,"version":"3.51.4"},"reference-count":43,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,3,4]],"date-time":"2016-03-04T00:00:00Z","timestamp":1457049600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R24 DA018055"],"award-info":[{"award-number":["R24 DA018055"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmacology Res &amp; Perspec"],"published-print":{"date-parts":[[2016,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Naproxen (<jats:styled-content style=\"fixed-case\">NAP<\/jats:styled-content>) is a potent nonsteroidal anti\u2010inflammatory drug (<jats:styled-content style=\"fixed-case\">NSAID<\/jats:styled-content>) with a favorable cardiovascular profile. However, its long\u2010term use may lead to serious gastrointestinal and renal side effects. <jats:styled-content style=\"fixed-case\">NOSH<\/jats:styled-content>\u2010 (nitric oxide and hydrogen sulfide) releasing naproxen (<jats:styled-content style=\"fixed-case\">NOSH<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">NAP<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> AVT<\/jats:styled-content>\u2010219) belongs to a new class of anti\u2010inflammatory agents designed to overcome these limitations. We compared the gastrointestinal safety, anti\u2010inflammatory, analgesic, antipyretic, and antiplatelet properties of <jats:styled-content style=\"fixed-case\">AVT<\/jats:styled-content>\u2010219 to that of <jats:styled-content style=\"fixed-case\">NAP<\/jats:styled-content> in preclinical animal models. We also evaluated its anticancer effects in 11 human cancer cell (<jats:styled-content style=\"fixed-case\">HCC<\/jats:styled-content>) lines of six different tissue origins and in a chemotherapeutic xenograft mouse model of colon cancer. <jats:styled-content style=\"fixed-case\">AVT<\/jats:styled-content>\u2010219: (1) was orders of magnitude more potent than <jats:styled-content style=\"fixed-case\">NAP<\/jats:styled-content> in inhibiting the growth of cultured <jats:styled-content style=\"fixed-case\">HCC<\/jats:styled-content>; (2) was safe to the stomach, whereas <jats:styled-content style=\"fixed-case\">NAP<\/jats:styled-content> caused significant ulceration; (3) showed strong anti\u2010inflammatory, analgesic, antipyretic, and antiplatelet properties comparable to <jats:styled-content style=\"fixed-case\">NAP<\/jats:styled-content>; and (4) <jats:styled-content style=\"fixed-case\">NAP<\/jats:styled-content> caused a significant rise in plasma tumor necrosis factor\u2010alpha (<jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\u03b1), whereas in the <jats:styled-content style=\"fixed-case\">AVT<\/jats:styled-content>\u2010219\u2010treated rats this rise was significantly less. Mechanistically, <jats:styled-content style=\"fixed-case\">AVT<\/jats:styled-content>\u2010219 was a strong antioxidant, inhibited cyclooxygenase (<jats:styled-content style=\"fixed-case\">COX<\/jats:styled-content>)\u20101 and \u20102, thus reducing prostaglandin (<jats:styled-content style=\"fixed-case\">PG<\/jats:styled-content>) E<jats:sub>2<\/jats:sub>. In xenografts, <jats:styled-content style=\"fixed-case\">AVT<\/jats:styled-content>\u2010219 significantly reduced tumor growth and tumor mass with no sign of <jats:styled-content style=\"fixed-case\">GI<\/jats:styled-content> toxicity, whereas <jats:styled-content style=\"fixed-case\">NAP<\/jats:styled-content>\u2010treated mice died due to <jats:styled-content style=\"fixed-case\">GI<\/jats:styled-content> bleeding. <jats:styled-content style=\"fixed-case\">AVT<\/jats:styled-content>\u2010219 displayed considerable safety and potency in inhibiting <jats:styled-content style=\"fixed-case\">HCC<\/jats:styled-content> growth; was an effective analgesic, antipyretic, antiplatelet, and anti\u2010inflammatory; and was significantly more efficacious than <jats:styled-content style=\"fixed-case\">NAP<\/jats:styled-content> in reducing the growth of established tumors in a xenograft mouse model.<\/jats:p>","DOI":"10.1002\/prp2.224","type":"journal-article","created":{"date-parts":[[2016,3,6]],"date-time":"2016-03-06T03:32:13Z","timestamp":1457235133000},"source":"Crossref","is-referenced-by-count":40,"title":["Gastrointestinal safety, chemotherapeutic potential, and classic pharmacological profile of <scp>NOSH<\/scp>\u2010naproxen (<scp>AVT<\/scp>\u2010219) a dual <scp>NO\u2010<\/scp> and H<sub>2<\/sub>S\u2010releasing hybrid"],"prefix":"10.1002","volume":"4","author":[{"given":"Mitali","family":"Chattopadhyay","sequence":"first","affiliation":[{"name":"Department of Physiology, Pharmacology and Neuroscience Sophie Davis School of Biomedical Education City University of New York School of Medicine New York NY 10031"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ravinder","family":"Kodela","sequence":"additional","affiliation":[{"name":"Department of Physiology, Pharmacology and Neuroscience Sophie Davis School of Biomedical Education City University of New York School of Medicine New York NY 10031"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pascale L.","family":"Duvalsaint","sequence":"additional","affiliation":[{"name":"Department of Physiology, Pharmacology and Neuroscience Sophie Davis School of Biomedical Education City University of New York School of Medicine New York NY 10031"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khosrow","family":"Kashfi","sequence":"additional","affiliation":[{"name":"Department of Physiology, Pharmacology and Neuroscience Sophie Davis School of Biomedical Education City University of New York School of Medicine New York NY 10031"},{"name":"Avicenna Pharmaceuticals Inc. 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