{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T07:40:57Z","timestamp":1761896457294,"version":"build-2065373602"},"reference-count":19,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2017,4,3]],"date-time":"2017-04-03T00:00:00Z","timestamp":1491177600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Austrian Research Promotion Agency","award":["812095-SCK\/SAI","820121\/18793 SCK\/KUG"],"award-info":[{"award-number":["812095-SCK\/SAI","820121\/18793 SCK\/KUG"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2017,8]]},"abstract":"\n Aims<\/jats:title>\n \n 55P0251<\/jats:styled-content>\n is a novel compound with blood glucose lowering activity in mice, which has been developed from a molecular backbone structure found in herbal remedies. We here report its basic pharmacological attributes and initial progress in unmasking the mode of action.\n <\/jats:p>\n <\/jats:sec>\n \n Materials and methods<\/jats:title>\n \n Pharmacokinetic properties of\n 55P0251<\/jats:styled-content>\n were portrayed in several species. First efforts to elucidate the glucose lowering mechanism in rodents included numerous experimental protocols dealing with glucose tolerance, insulin secretion from isolated pancreatic islets and comparison to established drugs.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n A single oral dose of\n 55P0251<\/jats:styled-content>\n improved glucose tolerance in mice with an\n \n ED\n 50<\/jats:sub>\n <\/jats:styled-content>\n between 1.5 and 2\u2009mg\/kg (reductions in areas under the curve, 1\u2009mg\/kg, \u221218%; 5\u2009mg\/kg, \u221230%; 27\u2009mg\/kg, \u221247%). Pharmacokinetic studies revealed attractive attributes, including a plasma half\u2010life of approximately 3\u2009hours and a bioavailability of approximately 58% in rats.\n 55P0251<\/jats:styled-content>\n amplified glucose stimulated insulin release from isolated mouse islets and improved glucose tolerance via increased insulin secretion in rats (increase in area under the insulin curve, +184%). Unlike sulfonylureas and glinides,\n 55P0251<\/jats:styled-content>\n hardly stimulated insulin release under basal conditions and did not induce hypoglycaemia\n in vivo<\/jats:italic>\n , but it amplified the secretory response to glucose and other insulinotropic stimuli (\n KCl<\/jats:styled-content>\n , glucagon\u2010like peptide\u20101). Comparison to established anti\u2010diabetic agents and examination of interaction with molecular targets (\n \n K\n ATP<\/jats:sub>\n <\/jats:styled-content>\n channel, dipeptidyl peptidase\u20104, glucagon\u2010like peptide\u20101 receptor) excluded molecular mechanisms addressed by presently marketed drugs.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n 55P0251<\/jats:styled-content>\n is a novel compound that potently counteracts hyperglycaemia in rodents via amplification of glucose\u2010stimulated insulin release.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/dom.12914","type":"journal-article","created":{"date-parts":[[2017,2,17]],"date-time":"2017-02-17T07:26:39Z","timestamp":1487316399000},"page":"1088-1096","source":"Crossref","is-referenced-by-count":2,"title":["Preclinical characterization of\n 55P0251<\/scp>\n , a novel compound that amplifies glucose\u2010stimulated insulin secretion and counteracts hyperglycaemia in rodents"],"prefix":"10.1111","volume":"19","author":[{"given":"Karin","family":"Stadlbauer","sequence":"first","affiliation":[{"name":"Division of Endocrinology & Metabolism, Department of Medicine III Medical University of Vienna Vienna Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Brunmair","sequence":"additional","affiliation":[{"name":"Division of Endocrinology & Metabolism, Department of Medicine III Medical University of Vienna Vienna Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zsuzsanna","family":"Lehner","sequence":"additional","affiliation":[{"name":"Division of Endocrinology & Metabolism, Department of Medicine III Medical University of Vienna Vienna Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Immanuel","family":"Adorjan","sequence":"additional","affiliation":[{"name":"55pharma Drug Discovery & Development AG Vienna Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Scherer","sequence":"additional","affiliation":[{"name":"Division of Endocrinology & Metabolism, Department of Medicine III Medical University of Vienna Vienna Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anton","family":"Luger","sequence":"additional","affiliation":[{"name":"Division of Endocrinology & Metabolism, Department of Medicine III Medical University of Vienna Vienna Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonhardt","family":"Bauer","sequence":"additional","affiliation":[{"name":"55pharma Drug Discovery & Development AG Vienna Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7168-0013","authenticated-orcid":false,"given":"Clemens","family":"F\u00fcrnsinn","sequence":"additional","affiliation":[{"name":"Division of Endocrinology & Metabolism, Department of Medicine III Medical University of Vienna Vienna Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,4,3]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm0704090"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/np200906s"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.EPX.0000440994.89503.45"},{"key":"e_1_2_5_5_1","first-page":"197","volume-title":"Methods in Plant Biochemistry","author":"Wink M","year":"1993"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2006-962797"},{"key":"e_1_2_5_7_1","first-page":"484","volume-title":"Lupins for Health and Wealth","author":"Gurrola\u2010D\u00edaz CM","year":"2008"},{"key":"e_1_2_5_8_1","first-page":"565","article-title":"Influence of dietary lupin seed mixed diet on serum cholesterol level in normal and diabetic rabbits","volume":"34","author":"Ahmed RT","year":"1993","journal-title":"Egypt 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