| Ligand-Based Structural Optimization of Grb2-SH2 Inhibitors: High Affinity, Low Charge and Reduced Peptidic Nature | |
| Alternative Title | Ligand-Based Structural Optimization of Grb2-SH2 Inhibitors: High Affinity, Low Charge and Reduced Peptidic Nature |
| Peng Dian1; Zhi Ying1; Xue Ting1; Gao Huiyuan2; Long Yaqiu1 | |
| 2011 | |
| Source Publication | CHINESE JOURNAL OF ORGANIC CHEMISTRY
 |
| ISSN | 0253-2786 |
| Volume | 31Issue:12Pages:2019-2033 |
| Abstract | 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. |
| Keyword | STRUCTURE-BASED DESIGN RING-CLOSING METATHESIS SH2 DOMAIN NONPHOSPHORYLATED INHIBITOR PHOSPHOTYROSYL MIMETICS ACID-RESIDUES BINDING ANTAGONISTS POSITION REQUIREMENTS phosphotyrosine Grb2-SH2 inhibitor structure-activity relationship mitogenic ras pathway anti-tumor drug |
| Indexed By | CSCD |
| Language | 英语 |
| CSCD ID | CSCD:4413751 |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | http://ir.imr.ac.cn/handle/321006/153851 |
| Collection | 中国科学院金属研究所 |
| Affiliation | 1.中国科学院 2.中国科学院金属研究所 |
| Recommended Citation 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. |
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