Benzbromarone, an old uricosuric drug, inhibits human fatty acid binding protein 4 in vitro and lowers the blood glucose level in db/db mice
文献类型：期刊论文
| 作者 | Cai, Hai-yan1,2; Wang, Ting1; Zhao, Jian-chun3; Sun, Peng1; Yan, Gui-rui1; Ding, Hai-peng2; Li, Ying-xia3; Wang, He-yao1 ; Zhu, Wei-liang1; Chen, Kai-xian1
|
| 刊名 | ACTA PHARMACOLOGICA SINICA
 |
| 出版日期 | 2013-11 |
| 卷号 | 34期号:11页码:1397-1402 |
| ISSN号 | 1671-4083 |
| 关键词 | benzbromarone uricosuric drug fatty acid-binding protein 4 adipocyte diabetes db/db mouse molecular docking |
| DOI | 10.1038/aps.2013.97 |
| 文献子类 | Article |
| 英文摘要 | Aim: Fatty acid-binding protein 4 (FABP4) plays an important role in maintaining glucose and lipid homeostasis. The aim of this study was to find new inhibitors of FABP4 for the treatment of type 2 diabetes. Methods: Human FABP4 protein was expressed, and its inhibitors were detected in 1,8-ANS displacement assay. The effect of the inhibitor on lipolysis activity was examined in mouse 3T3-L1 preadipocytes. The db/db mice were used to evaluate the anti-diabetic activity of the inhibitor. Molecular docking and site-directed mutagenesis studies were carried out to explore the binding mode between the inhibitor and FABP4. Results: From 232 compounds tested, benzbromarone (BBR), an old uricosuric drug, was discovered to be the best inhibitor of FABP4 with an IC50 value of 14.8 mu mol/L. Furthermore, BBR (25 mu mol/L) significantly inhibited forskolin-stimulated lipolysis in 3T3-L1 cells. Oral administration of BBR (25 or 50 mg/kg, for 4 weeks) dose-dependently reduced the blood glucose level and improved glucose tolerance and insulin resistance in db/db mice. Molecular docking revealed that the residues Ser55, Asp76, and Arg126 of FABP4 formed important interactions with BBR, which was confirmed by site-directed mutagenesis studies. Conclusion: BBR is an inhibitor of FABP4 and a potential drug candidate for the treatment of type 2 diabetes and atherosclerosis. |
| WOS关键词 | BODY-WEIGHT GAIN ; AP2 ; EXPRESSION ; ATHEROSCLEROSIS ; LIPOLYSIS ; RISK ; GENE ; GOUT |
| 资助项目 | National Natural Science Foundation of China[20721003] ; National Natural Science Foundation of China[81072681] ; International ST Cooperation[2010DFB73280] ; National 863 High Performance Computing Project, China[2012AA01A305] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| CSCD记录号 | CSCD:4966493 |
| 出版者 | ACTA PHARMACOLOGICA SINICA |
| WOS记录号 | WOS:000326680500005 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277397]  |
| 专题 | 药理学第三研究室 药物发现与设计中心 |
| 通讯作者 | Wang, He-yao |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 2.Tongji Univ, Sch Life Sci & Technol, Adv Inst Translat Med, Shanghai 200092, Peoples R China; 3.Fudan Univ, Sch Pharm, Dept Med Chem, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Cai, Hai-yan,Wang, Ting,Zhao, Jian-chun,et al. Benzbromarone, an old uricosuric drug, inhibits human fatty acid binding protein 4 in vitro and lowers the blood glucose level in db/db mice[J]. ACTA PHARMACOLOGICA SINICA,2013,34(11):1397-1402. |
| APA | Cai, Hai-yan.,Wang, Ting.,Zhao, Jian-chun.,Sun, Peng.,Yan, Gui-rui.,...&Chen, Kai-xian.(2013).Benzbromarone, an old uricosuric drug, inhibits human fatty acid binding protein 4 in vitro and lowers the blood glucose level in db/db mice.ACTA PHARMACOLOGICA SINICA,34(11),1397-1402. |
| MLA | Cai, Hai-yan,et al."Benzbromarone, an old uricosuric drug, inhibits human fatty acid binding protein 4 in vitro and lowers the blood glucose level in db/db mice".ACTA PHARMACOLOGICA SINICA 34.11(2013):1397-1402. |
入库方式： OAI收割
来源：上海药物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。