Combined Virtual Screening and Substructure Search for Discovery of Novel FABP4 Inhibitors
文献类型：期刊论文
| 作者 | Cai, Haiyan1,2; Wang, Ting2; Yang, Zhuo3; Xu, Zhijian2 ; Wang, Guimin2; Wang, He-Yao2; Zhu, Weiliang2; Chen, Kaixian2
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| 刊名 | JOURNAL OF CHEMICAL INFORMATION AND MODELING
 |
| 出版日期 | 2017-09 |
| 卷号 | 57期号:9页码:2329-2335 |
| ISSN号 | 1549-9596 |
| DOI | 10.1021/acs.jcim.7b00364 |
| 文献子类 | Article |
| 英文摘要 | Fatty acid-binding protein 4 (FABP4, AFABP) is a potential drug target for diabetes and atherosclerosis. In this study, a series of novel FABP4 inhibitors were discovered through combining virtual screening and substructure search. Seventeen compounds exhibited FABP4 inhibitory activities with IC50 < 10 mu M, among which 11 compounds showed high selectivity against FABP3. The best compound 36b displayed an IC50 value of 1.5 mu M. Molecular docking and point mutation studies revealed that Gln95, Arg126, and Tyr128 play key roles for these compounds binding with FABP4. Interestingly, Gln95 seems to be essential for conformation stability of FABP4. The new scaffolds of these compounds and their interaction mechanisms binding with FABP4 should provide an important clue for the further development of novel FABP4 inhibitors. |
| WOS关键词 | ACID-BINDING PROTEIN ; ACCURATE DOCKING ; AP2 ; MICE ; ATHEROSCLEROSIS ; DRUG ; METABOLISM ; GLUCOSE ; OBESITY ; TARGET |
| 资助项目 | National Natural Science Foundation of China[81473262] ; National Natural Science Foundation of China[81502981] ; National Natural Science Foundation of China[81573350] ; NSFC-Guangdong Joint Fund[U1501501] ; Institutes for Drug Discovery and Development, Chinese Academy of Sciences[CASIMM0120162025] ; Institutes for Drug Discovery and Development, Chinese Academy of Sciences[CA-SIMM0120164014] |
| WOS研究方向 | Pharmacology & Pharmacy ; Chemistry ; Computer Science |
| 语种 | 英语 |
| WOS记录号 | WOS:000411914200020 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/272502]  |
| 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; Zhu, Weiliang |
| 作者单位 | 1.Shanghai Jiao Tong Univ, Dept Pathophysiol, Key Lab Cell Differentiat & Apoptosis, Chinese Minist Educ,Sch Med, Shanghai 200025, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China; 3.Chinese Acad Sci, Chem Biol Core Facil, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China |
| 推荐引用方式 GB/T 7714 | Cai, Haiyan,Wang, Ting,Yang, Zhuo,et al. Combined Virtual Screening and Substructure Search for Discovery of Novel FABP4 Inhibitors[J]. JOURNAL OF CHEMICAL INFORMATION AND MODELING,2017,57(9):2329-2335. |
| APA | Cai, Haiyan.,Wang, Ting.,Yang, Zhuo.,Xu, Zhijian.,Wang, Guimin.,...&Chen, Kaixian.(2017).Combined Virtual Screening and Substructure Search for Discovery of Novel FABP4 Inhibitors.JOURNAL OF CHEMICAL INFORMATION AND MODELING,57(9),2329-2335. |
| MLA | Cai, Haiyan,et al."Combined Virtual Screening and Substructure Search for Discovery of Novel FABP4 Inhibitors".JOURNAL OF CHEMICAL INFORMATION AND MODELING 57.9(2017):2329-2335. |
入库方式： OAI收割
来源：上海药物研究所
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