Ligand-Based Structural Optimization of Grb2-SH2 Inhibitors: High Affinity, Low Charge and Reduced Peptidic Nature
文献类型：期刊论文
| 作者 | Peng Dian1,2; Zhi Ying1; Xue Ting1; Gao Huiyuan2; Long Yaqiu1 |
| 刊名 | CHINESE JOURNAL OF ORGANIC CHEMISTRY
 |
| 出版日期 | 2011-12 |
| 卷号 | 31期号:12页码:2019-2033 |
| 关键词 | phosphotyrosine Grb2-SH2 inhibitor structure-activity relationship mitogenic ras pathway anti-tumor drug |
| ISSN号 | 0253-2786 |
| 文献子类 | Article |
| 英文摘要 | The growth factor receptor bound protein 2 (Grb2) is an intracellular adaptor protein. By its SH2 domain binding to the specific pTyr containing motif on the activated EGFR, Grb2 triggers the downstream activation of mitogenic Ras pathways which have been implicated in the etiology of certain breast cancers. So Grb2-SH2 has been recognized as an excellent target for the antitumor drug design. In this article, the recent progress of Grb2-SH2 inhibitors is reviewed, focused on the strategy to overcome the problems of the high charge and the low bioavailability endowed by the essential phosphotyrosine and the peptidic nature, respectively. The systematic structure-activity relationship study and the rational structural optimization were achieved based on the ligand-protein interaction to improve the potency and simplify the molecular structure, providing useful information for the future development of phosphotyrosine-mediated SH2 signaling inhibitors into antitumor agents. |
| WOS关键词 | STRUCTURE-BASED DESIGN ; RING-CLOSING METATHESIS ; CONSTRAINED PHOSPHOTYROSYL MIMETICS ; DOMAIN-BINDING MACROCYCLES ; ALPHA-AMINO-ACIDS ; SH2 DOMAIN ; NONPHOSPHORYLATED INHIBITOR ; PHOSPHOPEPTIDE LIGANDS ; TYROSINE DERIVATIVES ; SIGNAL-TRANSDUCTION |
| WOS研究方向 | Chemistry |
| 语种 | 中文 |
| CSCD记录号 | CSCD:4413751 |
| WOS记录号 | WOS:000299064500006 |
| 出版者 | SCIENCE PRESS |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278307]  |
| 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 |
| 通讯作者 | Peng Dian |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 2.Shenyang Pharmaceut Univ, Sch Tradit Chinese Med, Shenyang 110016, Peoples R China |
| 推荐引用方式 GB/T 7714 | Peng Dian,Zhi Ying,Xue Ting,et al. Ligand-Based Structural Optimization of Grb2-SH2 Inhibitors: High Affinity, Low Charge and Reduced Peptidic Nature[J]. CHINESE JOURNAL OF ORGANIC CHEMISTRY,2011,31(12):2019-2033. |
| APA | Peng Dian,Zhi Ying,Xue Ting,Gao Huiyuan,&Long Yaqiu.(2011).Ligand-Based Structural Optimization of Grb2-SH2 Inhibitors: High Affinity, Low Charge and Reduced Peptidic Nature.CHINESE JOURNAL OF ORGANIC CHEMISTRY,31(12),2019-2033. |
| MLA | Peng Dian,et al."Ligand-Based Structural Optimization of Grb2-SH2 Inhibitors: High Affinity, Low Charge and Reduced Peptidic Nature".CHINESE JOURNAL OF ORGANIC CHEMISTRY 31.12(2011):2019-2033. |
入库方式： OAI收割
来源：上海药物研究所
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