{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T12:10:31Z","timestamp":1784635831657,"version":"3.55.0"},"reference-count":22,"publisher":"Walter de Gruyter GmbH","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"j_jbcpp-2025-0147_abs_001\">\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Sodium-glucose co-transporter 2 (SGLT2) inhibitors are a class of anti-diabetic drugs with cardiovascular benefits independent of glycemic control, partly via endothelial protection. Identifying novel inhibitors with both high affinity and vascular-protective effects remains a priority.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_jbcpp-2025-0147_abs_002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Structure-based high-throughput virtual screening (HTVS) of 14 million ligands was performed using Schr\u00f6dinger Glide. Compounds with better docking scores than empagliflozin (\u221213.615) were filtered for ADME properties using QikProp. Ten lead compounds were evaluated in human coronary artery endothelial cells under diabetic and ischemia-reperfusion (I\/R) models. Assays included glucose uptake, cytotoxicity (LDH), oxidative stress (ROS), and nitrosative stress\u00a0(NO).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_jbcpp-2025-0147_abs_003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Compound #7 demonstrated the most potent activity, reducing glucose uptake by 55\u202f% (p&lt;0.01), ROS by 48\u202f% (p&lt;0.05), and NO by 47\u202f% (p&lt;0.05). LDH release decreased 16\u202f% under diabetic stress and 20\u202f% under I\/R injury (both p&lt;0.05).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_jbcpp-2025-0147_abs_004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Compound #7 is a novel SGLT2 inhibitor with dual glucose-lowering and endothelial-protective effects. These findings highlight the utility of HTVS for rapid lead identification and support further development of compound #7 as a potential therapeutic agent targeting metabolic and vascular complications of diabetes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1515\/jbcpp-2025-0147","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T13:00:38Z","timestamp":1778677238000},"page":"305-314","source":"Crossref","is-referenced-by-count":0,"title":["Novel SGLT2 inhibitors with endothelial-protective potential: a combined computational and experimental approach"],"prefix":"10.1515","volume":"37","author":[{"given":"Jarritt","family":"Romanik","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences and Department of Chemistry , University of Saint Joseph , West Hartford , CT , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Gardella","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences and Department of Chemistry , University of Saint Joseph , West Hartford , CT , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"Dematteo","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences and Department of Chemistry , University of Saint Joseph , West Hartford , CT , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiru","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences and Department of Chemistry , University of Saint Joseph , West Hartford , CT , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Moy","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences and Department of Chemistry , University of Saint Joseph , West Hartford , CT , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asher","family":"Brandt","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences and Department of Chemistry , University of Saint Joseph , West Hartford , CT , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0095-3587","authenticated-orcid":false,"given":"Zhao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences and Department of Chemistry , University of Saint Joseph , West Hartford , CT , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2026,5,14]]},"reference":[{"key":"2026072111574562946_j_jbcpp-2025-0147_ref_001","unstructured":"Federation, ID. 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