Discovery of novel PTP1B inhibitors with antihyperglycemic activity
文献类型：期刊论文
| 作者 | Liu, Zhang1; Chai, Qian1; Li, Yuan-yuan2; Shen, Qiang2; Ma, Lan-ping1 ; Zhang, Li-na2; Wang, Xin1; Sheng, Li2; Li, Jing-ya2; Li, Jia2
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| 刊名 | ACTA PHARMACOLOGICA SINICA
 |
| 出版日期 | 2010-08 |
| 卷号 | 31期号:8页码:1005-1012 |
| 关键词 | protein tyrosine phosphatases (PTPs) diabetes antihyperglycemic activity drug screening |
| ISSN号 | 1671-4083 |
| DOI | 10.1038/aps.2010.81 |
| 文献子类 | Article |
| 英文摘要 | Aim: To discover and optimize a series of novel PTP1B inhibitors containing a thiazolidinone-substituted biphenyl scaffold and to further evaluate the inhibitory effects of these compounds in vitro and in vivo. Methods: A total of 36 thiazolidinone substituted biphenyl scaffold derivatives were prepared. An in vitro biological evaluation was done by Enzyme-based assay. The in vivo efficacy of 7Fb as an antihyperglycemic agent was evaluated in a BKS db/db diabetic mouse model with a dose of 50 mg.kg(-1).d(-1) for 4 weeks. Results: The in vitro biological evaluation showed that compounds 7Fb and 7Fc could increase the insulin-induced tyrosine phosphorylation of IR beta in CHO/hIR cells. In in vivo experiments, compound 7Fb significantly lowered the postprandial blood glucose, from 29.4 +/- 1.2 mmol/L with the vehicle to 24.7 +/- 0.6 mmol/L (P<0.01), and the fasting blood glucose from 27.3 +/- 1.5 mmol/L with the vehicle to 23.6 +/- 1.2 mmol/L (P<0.05). Conclusion: A novel series of compounds were discovered to be PTP1B inhibitors. Among them, compound 7Fb significantly lowered the postprandial and fasting glucose levels, and the blood glucose level declined more rapidly than in metformin-treated mice. Thus, 7Fb may be a potential lead compound for developing new agents for the treatment of type II diabetes. |
| WOS关键词 | PROTEIN-TYROSINE PHOSPHATASES ; INSULIN SENSITIVITY ; 1B ; MICE ; SPECIFICITY ; RESISTANCE ; GLUCOSE ; ACID |
| 资助项目 | 863 High-Tech Research and Development Program of China[2006AA02Z315] ; 863 High-Tech Research and Development Program of China[2008AA02Z105] ; National S&T Major Projects "Key New Drug Creation and Manufacturing Program" of China[2009ZX09301-001] ; National S&T Major Projects "Key New Drug Creation and Manufacturing Program" of China[2009ZX09302-001] ; National S&T Major Projects "Key New Drug Creation and Manufacturing Program" of China[2009ZX09501-010] ; Public Service Platform Foundation of Shanghai Ministry of Science and Technology[08DZ2291300] ; Public Service Platform Foundation of Shanghai Ministry of Science and Technology[09DZ2291200] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| CSCD记录号 | CSCD:3971261 |
| WOS记录号 | WOS:000280617100016 |
| 出版者 | SHANGHAI INST MATERIA MEDICA |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278806]  |
| 专题 | 药物化学研究室 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 国家新药筛选中心 |
| 通讯作者 | Ma, Lan-ping |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Liu, Zhang,Chai, Qian,Li, Yuan-yuan,et al. Discovery of novel PTP1B inhibitors with antihyperglycemic activity[J]. ACTA PHARMACOLOGICA SINICA,2010,31(8):1005-1012. |
| APA | Liu, Zhang.,Chai, Qian.,Li, Yuan-yuan.,Shen, Qiang.,Ma, Lan-ping.,...&Shen, Jing-kang.(2010).Discovery of novel PTP1B inhibitors with antihyperglycemic activity.ACTA PHARMACOLOGICA SINICA,31(8),1005-1012. |
| MLA | Liu, Zhang,et al."Discovery of novel PTP1B inhibitors with antihyperglycemic activity".ACTA PHARMACOLOGICA SINICA 31.8(2010):1005-1012. |
入库方式： OAI收割
来源：上海药物研究所
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