{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T07:34:05Z","timestamp":1777448045793,"version":"3.51.4"},"reference-count":39,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2015,4,23]],"date-time":"2015-04-23T00:00:00Z","timestamp":1429747200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Exp Pharma Physio"],"published-print":{"date-parts":[[2015,5]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Vascular endothelial growth factor (<jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content>) is an important cerebral angiogenic and permeability factor under hypoxia. There is a need to find effective molecules that may ameliorate hypoxia\u2010induced cerebral oedema. <jats:italic>In silico<\/jats:italic> identification of novel candidate molecules that block <jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">A<\/jats:styled-content> site were identified and validated with a <jats:styled-content style=\"fixed-case\">R<\/jats:styled-content>amachandran plot. The active site residues of <jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">A<\/jats:styled-content> were detected by <jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>ocketfinder, <jats:styled-content style=\"fixed-case\">CAST<\/jats:styled-content>p, and <jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>og<jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>ite<jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>corer. Based on <jats:italic>in silico<\/jats:italic> data, three <jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">A<\/jats:styled-content> blocker (<jats:styled-content style=\"fixed-case\">VAB<\/jats:styled-content>) candidate molecules (<jats:styled-content style=\"fixed-case\">VAB<\/jats:styled-content>1, <jats:styled-content style=\"fixed-case\">VAB<\/jats:styled-content>2, and <jats:styled-content style=\"fixed-case\">VAB<\/jats:styled-content>3) were checked for improvement in cellular viability and regulation of <jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content> levels in <jats:styled-content style=\"fixed-case\">N<\/jats:styled-content>2a cells under hypoxia (0.5% O<jats:sub>2<\/jats:sub>). Additionally, the best candidate molecule's efficacy was assessed in male <jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>prague\u2010<jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>awley rats for its ameliorative effect on cerebral oedema and vascular leakage under hypobaric hypoxia 7260 m. All experimental results were compared with the commercially available <jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content> blocker sunitinib. Vascular endothelial growth factor\u2010<jats:styled-content style=\"fixed-case\">A<\/jats:styled-content> blocker 1 was found most effective in increasing cellular viability and maintaining normal <jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content> levels under hypoxia (0.5% oxygen) in <jats:styled-content style=\"fixed-case\">N<\/jats:styled-content>2a cells. Vascular endothelial growth factor\u2010<jats:styled-content style=\"fixed-case\">A<\/jats:styled-content> blocker 1 effectively restored <jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content> levels, decreased cerebral oedema, and reduced vascular leakage under hypobaric hypoxia when compared to sunitinib\u2010treated rats. Vascular endothelial growth factor\u2010<jats:styled-content style=\"fixed-case\">A<\/jats:styled-content> blocker 1 may be a promising candidate molecule for ameliorating hypobaric hypoxia\u2010induced vasogenic oedema by regulating <jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content> levels.<\/jats:p>","DOI":"10.1111\/1440-1681.12387","type":"journal-article","created":{"date-parts":[[2015,3,4]],"date-time":"2015-03-04T15:01:38Z","timestamp":1425481298000},"page":"475-484","source":"Crossref","is-referenced-by-count":10,"title":["Novel vascular endothelial growth factor blocker improves cellular viability and reduces hypobaric hypoxia\u2010induced vascular leakage and oedema in rat brain"],"prefix":"10.1111","volume":"42","author":[{"given":"Deepika","family":"Saraswat","sequence":"first","affiliation":[{"name":"Department of Experimental Biology Defence Institute of Physiology and Allied Science Defence Research and Development Organization New Delhi India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarita","family":"Nehra","sequence":"additional","affiliation":[{"name":"Department of Experimental Biology Defence Institute of Physiology and Allied Science Defence Research and Development Organization New Delhi India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kamal","family":"Chaudhary","sequence":"additional","affiliation":[{"name":"Division of Applied Sciences and Indo\u2010Russian Centre for Biotechnology [IRCB] Indian Institute of Information Technology Allahabad India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siva Prasad","family":"CVS","sequence":"additional","affiliation":[{"name":"Division of Applied Sciences and Indo\u2010Russian Centre for Biotechnology [IRCB] Indian Institute of Information Technology Allahabad India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,4,23]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpa.2011.02.008"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0004(03)00193-2"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.6026\/97320630010273"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2007.05.013"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1203855"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.theriogenology.2013.10.017"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0603-669"},{"key":"e_1_2_7_9_1","first-page":"444","article-title":"Vascular endothelial growth factor (VEGF) \u2013 part 1: In physiology and pathophysiology","volume":"62","author":"Kajdaniuk D","year":"2011","journal-title":"Endokrynol. 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