{"title":"将 AdipoRon 类似物鉴定为治疗 2 型糖尿病的新型 AMPK 激活剂","authors":"Chao Lin, Geng Sun and Yi Li","doi":"10.1039/D3MD00727H","DOIUrl":null,"url":null,"abstract":"<p >The activation of AMPK has emerged as a promising therapeutic approach for the treatment of metabolic diseases. AdipoRon, an agonist of the adiponectin receptor, has been identified as a compound capable of activating AMPK <em>via</em> the adiponectin receptor. To identify novel AdipoRon analogues with AMPK activation potential, a total of 17 analogues were designed, synthesized, and subjected to biological evaluation. Among these analogues, <strong>X-12</strong> was discovered to exhibit potent activation of AMPK. In experimental studies, <strong>X-12</strong> demonstrated dose-dependent improvements in glucose tolerance in normal mice. Furthermore, it significantly reduced fasting blood glucose levels and ameliorated insulin resistance in <em>db</em>/<em>db</em> diabetic mice. These findings highlight the therapeutic potential of <strong>X-12</strong> as a novel class of AMPK activators for the treatment of metabolic diseases.</p>","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":4.1000,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Identification of AdipoRon analogues as novel activators of AMPK for the treatment of type 2 diabetes†\",\"authors\":\"Chao Lin, Geng Sun and Yi Li\",\"doi\":\"10.1039/D3MD00727H\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >The activation of AMPK has emerged as a promising therapeutic approach for the treatment of metabolic diseases. AdipoRon, an agonist of the adiponectin receptor, has been identified as a compound capable of activating AMPK <em>via</em> the adiponectin receptor. To identify novel AdipoRon analogues with AMPK activation potential, a total of 17 analogues were designed, synthesized, and subjected to biological evaluation. Among these analogues, <strong>X-12</strong> was discovered to exhibit potent activation of AMPK. In experimental studies, <strong>X-12</strong> demonstrated dose-dependent improvements in glucose tolerance in normal mice. Furthermore, it significantly reduced fasting blood glucose levels and ameliorated insulin resistance in <em>db</em>/<em>db</em> diabetic mice. These findings highlight the therapeutic potential of <strong>X-12</strong> as a novel class of AMPK activators for the treatment of metabolic diseases.</p>\",\"PeriodicalId\":21462,\"journal\":{\"name\":\"RSC medicinal chemistry\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.1000,\"publicationDate\":\"2024-06-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"RSC medicinal chemistry\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://pubs.rsc.org/en/content/articlelanding/2024/md/d3md00727h\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"RSC medicinal chemistry","FirstCategoryId":"3","ListUrlMain":"https://pubs.rsc.org/en/content/articlelanding/2024/md/d3md00727h","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Identification of AdipoRon analogues as novel activators of AMPK for the treatment of type 2 diabetes†
The activation of AMPK has emerged as a promising therapeutic approach for the treatment of metabolic diseases. AdipoRon, an agonist of the adiponectin receptor, has been identified as a compound capable of activating AMPK via the adiponectin receptor. To identify novel AdipoRon analogues with AMPK activation potential, a total of 17 analogues were designed, synthesized, and subjected to biological evaluation. Among these analogues, X-12 was discovered to exhibit potent activation of AMPK. In experimental studies, X-12 demonstrated dose-dependent improvements in glucose tolerance in normal mice. Furthermore, it significantly reduced fasting blood glucose levels and ameliorated insulin resistance in db/db diabetic mice. These findings highlight the therapeutic potential of X-12 as a novel class of AMPK activators for the treatment of metabolic diseases.