New Insights into PI3K Inhibitor Design using X-ray Structures of PI3K alpha Complexed with a Potent Lead Compound
文献类型：期刊论文
| 作者 | Yang, Xiuyan2,3; Zhang, Xi4; Huang, Min3,5 ; Song, Kun3; Li, Xuefen4; Huang, Meilang1; Meng, Linghua4; Zhang, Jian2,3
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| 刊名 | SCIENTIFIC REPORTS
 |
| 出版日期 | 2017-11-06 |
| 卷号 | 7 |
| ISSN号 | 2045-2322 |
| DOI | 10.1038/s41598-017-15260-5 |
| 文献子类 | Article |
| 英文摘要 | Phosphatidylinositol 3-kinase a is an attractive target to potentially treat a range of cancers. Herein, we described the evolution of a reported PI3K inhibitor into a moderate PI3K alpha inhibitor with a low molecular weight. We used X-ray crystallography to describe the accurate binding mode of the compound YXY-4F. A comparison of the p110 alpha-YXY-4F and apo p110 alpha complexes showed that YXY-4F induced additional space by promoting a flexible conformational change in residues Ser773 and Ser774 in the PI3K alpha ATP catalytic site. Specifically, residue 773(S) in PI3K alpha is quite different from that of PI3K beta (D), gamma( A), and delta (D), which might guide further optimization of substituents around the NH group and phenyl group to improve the selectivity and potency of PI3K alpha. |
| WOS关键词 | PHOSPHOINOSITIDE 3-KINASE ALPHA ; RATIONAL DESIGN ; BREAST-CANCER ; PIK3CA GENE ; PATHWAY ; DISCOVERY ; MUTATIONS ; IDENTIFICATION ; CARCINOMA ; ISOFORM |
| 资助项目 | National Basic Research Program of China (973 Program)[2015CB910403] ; National Natural Science Foundation of China[81473137] ; National Natural Science Foundation of China[21702137] ; Shanghai Sailing Program[17YF1410600] ; National Program for Support of Top-notch Young Professionals[00000000] |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:000414415000072 |
| 出版者 | NATURE PUBLISHING GROUP |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/272412]  |
| 专题 | 药理学第一研究室 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 | Meng, Linghua; Zhang, Jian |
| 作者单位 | 1.Queens Univ, Sch Chem & Chem Engn, Belfast, Antrim, North Ireland; 2.Jiangsu Univ Technol, Sch Elect & Informat Engn, Inst Bioinformat & Med Engn, Changzhou 213001, Peoples R China; 3.Shanghai Jiao Tong Univ, Key Lab Cell Differentiat & Apoptosis Chinese, Chem Biol Div Shanghai Univ E Inst, Dept Pathophysiol,Minist Educ, Shanghai 200025, Peoples R China; 4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Div Anti Tumor Pharmacol, Shanghai 201203, Peoples R China; 5.Fourth Mil Med Univ, Xijing Hosp, Dept Hepatobiliary Surg, Xian, Shaanxi, Peoples R China |
| 推荐引用方式 GB/T 7714 | Yang, Xiuyan,Zhang, Xi,Huang, Min,et al. New Insights into PI3K Inhibitor Design using X-ray Structures of PI3K alpha Complexed with a Potent Lead Compound[J]. SCIENTIFIC REPORTS,2017,7. |
| APA | Yang, Xiuyan.,Zhang, Xi.,Huang, Min.,Song, Kun.,Li, Xuefen.,...&Zhang, Jian.(2017).New Insights into PI3K Inhibitor Design using X-ray Structures of PI3K alpha Complexed with a Potent Lead Compound.SCIENTIFIC REPORTS,7. |
| MLA | Yang, Xiuyan,et al."New Insights into PI3K Inhibitor Design using X-ray Structures of PI3K alpha Complexed with a Potent Lead Compound".SCIENTIFIC REPORTS 7(2017). |
入库方式： OAI收割
来源：上海药物研究所
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