From hit to lead: Structure-based discovery of naphthalene-1 sulfonamide derivatives as potent and selective inhibitors of fatty acid binding protein 4
文献类型：期刊论文
| 作者 | Gao, Ding-Ding2; Dou, Hui-Xia1,3; Su, Hai-Xia1,4; Zhang, Ming-Ming2; Wang, Ting3; Liu, Qiu-Feng4; Cai, Hai-Yan4,5; Ding, Hai-Peng2; Yang, Zhuo4; Zhu, Wei-Liang4
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| 刊名 | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
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| 出版日期 | 2018-06-25 |
| 卷号 | 154页码:44-59 |
| 关键词 | FABP4 inhibitors FABP3 sparing Structure-based design strategy X-ray crystallography |
| ISSN号 | 0223-5234 |
| DOI | 10.1016/j.ejmech.2018.05.007 |
| 文献子类 | Article |
| 英文摘要 | Fatty acid binding protein 4 (FABP4) plays a critical role in metabolism and inflammatory processes and therefore is a potential therapeutic target for immunometabolic diseases such as diabetes and atherosclerosis. Herein, we reported the identification of naphthalene-1-sulfonamide derivatives as novel, potent and selective FABP4 inhibitors by applying a structure-based design strategy. The binding affinities of compounds 16dk,16do and 16du to FABP4, at the molecular level, are equivalent to or even better than that of BMS309403. The X-ray crystallography complemented by the isothermal titration calorimetry studies revealed the binding mode of this series of inhibitors and the pivotal network of ordered water molecules in the binding pocket of FABP4. Moreover, compounds 16dk and 16do showed good metabolic stabilities in liver microsomes. Further extensive in vivo study demonstrated that 16dk and 16do exhibited a dramatic improvement in glucose and lipid metabolism, by decreasing fasting blood glucose and serum lipid levels, enhancing insulin sensitivity, and ameliorating hepatic steatosis in obese diabetic (db/db) mice. (C) 2018 Elsevier Masson SAS. All rights reserved. |
| WOS关键词 | MULTIGENE FAMILY ; CELL CARCINOMA ; PPAR-GAMMA ; EXPRESSION ; AP2 ; PROMOTES ; GENE ; ADIPOGENESIS ; FABPS ; MICE |
| 资助项目 | National Natural Science Foundation of China[81473075] ; National Natural Science Foundation of China[81473262] ; National Natural Science Foundation of China[81422047] ; National Key R&D Program of China[2016YFA0502301] ; Institutes for Drug Discovery and Development, Chinese Academy of Sciences[CASIMM0120164014] ; State Key Laboratory of Drug Research[SIMM1803KF-05] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000437551600004 |
| 出版者 | ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/279698]  |
| 专题 | 药物发现与设计中心 中科院受体结构与功能重点实验室 新药研究国家重点实验室 药理学第三研究室 |
| 通讯作者 | Zhu, Wei-Liang; Xu, Ye-Chun; Wang, He-Yao; Li, Ying-Xia |
| 作者单位 | 1.Univ Chinese Acad Sci, Beijing 100049, Peoples R China; 2.Fudan Univ, Sch Pharm, Shanghai 201203, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 4.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China; 5.Shanghai Jiao Tong Univ, Sch Med, Key Lab Cell Differentiat & Apoptosis, Dept Pathophysiol,Chinese Minist Educ, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Gao, Ding-Ding,Dou, Hui-Xia,Su, Hai-Xia,et al. From hit to lead: Structure-based discovery of naphthalene-1 sulfonamide derivatives as potent and selective inhibitors of fatty acid binding protein 4[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2018,154:44-59. |
| APA | Gao, Ding-Ding.,Dou, Hui-Xia.,Su, Hai-Xia.,Zhang, Ming-Ming.,Wang, Ting.,...&Li, Ying-Xia.(2018).From hit to lead: Structure-based discovery of naphthalene-1 sulfonamide derivatives as potent and selective inhibitors of fatty acid binding protein 4.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,154,44-59. |
| MLA | Gao, Ding-Ding,et al."From hit to lead: Structure-based discovery of naphthalene-1 sulfonamide derivatives as potent and selective inhibitors of fatty acid binding protein 4".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 154(2018):44-59. |
入库方式： OAI收割
来源：上海药物研究所
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