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The present study was designed to characterize the pharmacological profiles of CMD-05, a novel DPP-IV inhibitor discovered in our laboratory, <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>. The IC<jats:sub>50<\/jats:sub> of CMD-05 on DPP-IV inhibitory activity was approximately 12\u2009nM while vildagliptin was 3.5\u2009nM <jats:italic>in vitro<\/jats:italic>. In diabetes rat model established by high fat diet\/low dose streptozotocin, CMD-05 inhibited DPP-IV activity, significantly improved glucose tolerance, increased GLP-1 and insulin levels in plasma. Long-term administration of CMD-05 decreased HbA1c and TG levels and improved the islet function without significantly effect on body weight. Furthermore, CMD-05 reduced INS-1 cell apoptosis and increased GLP-1 secretion in NCI-H716. After oral administration, CMD-05 reached peak concentration at 30\u2009min with half-life of 288\u2009minutes and the inhibitory rate of DPP-IV greater than 50% lasted for 15\u2009h. In fasted normal rats, CMD-05 didn\u2019t cause significant hypoglycemia. CMD-05 had a lower cytotoxicity than vildagliptin <jats:italic>in vitro<\/jats:italic> and its maximum tolerance dose in mice is beyond 2000\u2009mg\/kg. These results indicated that CMD-05 has similar activity with vildagliptin <jats:italic>in vivo<\/jats:italic> and has a much longer half-life and lower cytotoxicity than vildagliptin.<\/jats:p>","DOI":"10.1038\/srep46628","type":"journal-article","created":{"date-parts":[[2017,4,13]],"date-time":"2017-04-13T09:23:17Z","timestamp":1492075397000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["CMD-05, a novel promising clinical anti-diabetic drug candidate, in vivo and vitro studies"],"prefix":"10.1038","volume":"7","author":[{"given":"Jie","family":"Ma","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huan","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangnan","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Congli","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhihao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyan","family":"Tian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Luo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Run","family":"Gan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junqing","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2017,4,13]]},"reference":[{"key":"BFsrep46628_CR1","doi-asserted-by":"crossref","first-page":"995","DOI":"10.2174\/156652412802480970","volume":"12","author":"L Chen","year":"2012","unstructured":"Chen, L., Klein, T. & Leung, P. 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