Identification of diverse dipeptidyl peptidase IV inhibitors via structure-based virtual screening
文献类型：期刊论文
| 作者 | Li, Cui2; Lu, Weiqiang2; Lu, Chunhua2; Xiao, Wen2; Shen, Xu1,2 ; Huang, Jin2; Liu, Guixia2; Tang, Yun2
|
| 刊名 | JOURNAL OF MOLECULAR MODELING
 |
| 出版日期 | 2012-09 |
| 卷号 | 18期号:9页码:4033-4042 |
| 关键词 | Dipeptidyl peptidase IV Molecular docking Pharmacophore modeling Type II diabetes Virtual screening |
| ISSN号 | 1610-2940 |
| DOI | 10.1007/s00894-012-1394-3 |
| 文献子类 | Article |
| 英文摘要 | Dipeptidyl peptidase IV (DPP4) is an important target for the treatment of type II diabetes mellitus. Inhibition of DPP4 will improve glycemic control in such patients by preventing the rapid breakdown and thereby prolonging the physiological actions of incretin hormones. Known DPP4 inhibitors (including marketed drugs and those drug candidates) appear to share similar structural features: the cyanopyrrolidine moieties, the xanthenes/pyrimidine parts and amino-like linkages. In this study, a multi-step virtual screening strategy including both rigid and flexible docking was employed to search for novel structures with DPP4 inhibition. From SPECS database, consisting of over 190,000 commercially available compounds, 99 virtual hits were picked up and 15 of them were eventually identified to have DPP4 inhibitory activities at 5 similar to 50 mu M. Diverse structures of our compounds were out of usual structural categories. Hence a pharmacophore model was built to further explore their common binding features on the enzyme. The results provided a new pathway for the discovery of DPP4 inhibitors and would be helpful for further optimization of DPP4 inhibitors. |
| WOS关键词 | GLUCOSE-TOLERANCE ; RATIONAL DESIGN ; DPP-4 INHIBITOR ; HIGHLY POTENT ; DISCOVERY ; AMIDES ; POLYPEPTIDE ; SITAGLIPTIN ; DEGRADATION ; MECHANISM |
| 资助项目 | National Natural Science Foundation of China[30973642] ; National Natural Science Foundation of China[90813005] ; Shanghai Committee of Science and Technology[11DZ2260600] ; Fundamental Research Funds for the Central Universities[0914035] ; Specialized Research Fund for the Doctoral Program of Higher Education of China[20090074120012] ; Shanghai Municipal Education Commission[10ZZ41] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Biophysics ; Chemistry ; Computer Science |
| 语种 | 英语 |
| WOS记录号 | WOS:000308114000004 |
| 出版者 | SPRINGER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277973]  |
| 专题 | 药理学第三研究室 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 |
| 通讯作者 | Huang, Jin |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 2.E China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Li, Cui,Lu, Weiqiang,Lu, Chunhua,et al. Identification of diverse dipeptidyl peptidase IV inhibitors via structure-based virtual screening[J]. JOURNAL OF MOLECULAR MODELING,2012,18(9):4033-4042. |
| APA | Li, Cui.,Lu, Weiqiang.,Lu, Chunhua.,Xiao, Wen.,Shen, Xu.,...&Tang, Yun.(2012).Identification of diverse dipeptidyl peptidase IV inhibitors via structure-based virtual screening.JOURNAL OF MOLECULAR MODELING,18(9),4033-4042. |
| MLA | Li, Cui,et al."Identification of diverse dipeptidyl peptidase IV inhibitors via structure-based virtual screening".JOURNAL OF MOLECULAR MODELING 18.9(2012):4033-4042. |
入库方式： OAI收割
来源：上海药物研究所
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