Fragment-based drug discovery of triazole inhibitors to block PDE delta-RAS protein-protein interaction
文献类型：期刊论文
| 作者 | Chen, Danqi1 ; Chen, Yuehong2; Lian, Fulin1; Chen, Liu1; Li, Yanlian1; Cao, Danyan1; Wang, Xin1; Chen, Lin1; Li, Jian1; Meng, Tao1
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| 刊名 | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
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| 出版日期 | 2019-02-01 |
| 卷号 | 163页码:597-609 |
| 关键词 | PDE delta-RAS Fragment-based Inhibitor Protein-protein interaction |
| ISSN号 | 0223-5234 |
| DOI | 10.1016/j.ejmech.2018.12.018 |
| 通讯作者 | Huang, Min(mhuang@simm.ac.cn) ; Zhang, Naixia(nxzhang@simm.ac.cn) ; Xiong, Bing(bxiong@simm.ac.cn) |
| 英文摘要 | Although mutated Ras protein is well recognized as an important drug target, direct targeting Ras has proven to be a daunting task. Recent studies demonstrated that Ras protein needs PDE delta to relocate to plasma membrane to execute its signaling transduction function, which provides a new avenue for modulating the Ras protein. To find small molecules antagonizing the interactions between PDE delta and Ras, here we presented a successful application of fragment-based drug discovery of PDE delta inhibitors. Under the guidance of crystal structures, we are able to quickly optimize the initial fragment into highly potent inhibitors, with more than 2000-fold improvement in binding activity, which further adds to the arsenal towards the inhibition of Ras signaling in cancer therapy. (C) 2018 Elsevier Masson SAS. All rights reserved. |
| WOS关键词 | KRAS |
| 资助项目 | National Natural Science Foundation of China[81330076] ; National Natural Science Foundation of China[81473094] ; National Natural Science Foundation of China[81402850] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12020345] ; Institutes for Drug Discovery and Development, Chinese Academy of Sciences[CASIMM0120164002] ; Institutes for Drug Discovery and Development, Chinese Academy of Sciences[CASIMM0120163013] ; Personalized Medicines Molecular Signature-based Drug Discovery and Development |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000458597300045 |
| 出版者 | ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/290469]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Huang, Min; Zhang, Naixia; Xiong, Bing |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Med Chem, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Div Antitumor Pharmacol, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Chen, Danqi,Chen, Yuehong,Lian, Fulin,et al. Fragment-based drug discovery of triazole inhibitors to block PDE delta-RAS protein-protein interaction[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2019,163:597-609. |
| APA | Chen, Danqi.,Chen, Yuehong.,Lian, Fulin.,Chen, Liu.,Li, Yanlian.,...&Xiong, Bing.(2019).Fragment-based drug discovery of triazole inhibitors to block PDE delta-RAS protein-protein interaction.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,163,597-609. |
| MLA | Chen, Danqi,et al."Fragment-based drug discovery of triazole inhibitors to block PDE delta-RAS protein-protein interaction".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 163(2019):597-609. |
入库方式： OAI收割
来源：上海药物研究所
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