Ligand-Based Structural Optimization of Grb2-SH2 Inhibitors: High Affinity, Low Charge and Reduced Peptidic Nature

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	Ligand-Based Structural Optimization of Grb2-SH2 Inhibitors: High Affinity, Low Charge and Reduced Peptidic Nature
其他题名	Ligand-Based Structural Optimization of Grb2-SH2 Inhibitors: High Affinity, Low Charge and Reduced Peptidic Nature
	Peng Dian 1; Zhi Ying 1; Xue Ting 1; Gao Huiyuan 2; Long Yaqiu 1
	2011
发表期刊	CHINESE JOURNAL OF ORGANIC CHEMISTRY
ISSN	0253-2786
卷号	31 期号:12 页码:2019-2033
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.
关键词	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
收录类别	CSCD
语种	英语
CSCD记录号	CSCD:4413751
引用统计
文献类型	期刊论文
条目标识符	http://ir.imr.ac.cn/handle/321006/153851
专题	中国科学院金属研究所
作者单位	1.中国科学院 2.中国科学院金属研究所
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.