Global S&T Development Trend Analysis Platform of Resources and Environment
DOI | 10.1126/science.aan4368 |
The target landscape of clinical kinase drugs | |
Klaeger, Susan1,2,3; Heinzlmeir, Stephanie1,2,3; Wilhelm, Mathias1; Polzer, Harald2,3,4; Vick, Binje2,3,5; Koenig, Paul-Albert6; Reinecke, Maria1,2,3; Ruprecht, Benjamin1; Petzoldt, Svenja1,2,3; Meng, Chen1; Zecha, Jana1,2,3; Reiter, Katrin2,3,4; Qiao, Huichao1; Helm, Dominic1; Koch, Heiner1,2,3; Schoof, Melanie1; Canevari, Giulia7; Casale, Elena7; Depaolini, Stefania Re7; Feuchtinger, Annette8; Wu, Zhixiang1; Schmidt, Tobias1; Rueckert, Lars9; Becker, Wilhelm9; Huenges, Jan9; Garz, Anne-Kathrin2,3,10; Gohlke, Bjoern-Oliver2,3,11; Zolg, Daniel Paul1; Kayser, Gian12; Vooder, Tonu13,14,15; Preissner, Robert2,3,11; Hahne, Hannes1; Tonisson, Neeme14,15; Kramer, Karl1; Goetze, Katharina2,3,10; Bassermann, Florian2,3,10; Schlegl, Judith16; Ehrlich, Hans-Christian9; Aiche, Stephan9; Walch, Axel8; Greif, Philipp A.2,3,4; Schneider, Sabine17,18; Felder, Eduard Rudolf7; Ruland, Juergen2,3,6; Medard, Guillaume1; Jeremias, Irmela2,5,19; Spiekermann, Karsten2,3,4; Kuster, Bernhard1,2,3,18,20 | |
2017-12-01 | |
发表期刊 | SCIENCE |
ISSN | 0036-8075 |
EISSN | 1095-9203 |
出版年 | 2017 |
卷号 | 358期号:6367 |
文章类型 | Article |
语种 | 英语 |
国家 | Germany; Italy; Estonia |
英文摘要 | Kinase inhibitors are important cancer therapeutics. Polypharmacology is commonly observed, requiring thorough target deconvolution to understand drug mechanism of action. Using chemical proteomics, we analyzed the target spectrum of 243 clinically evaluated kinase drugs. The data revealed previously unknown targets for established drugs, offered a perspective on the "druggable" kinome, highlighted (non)kinase off-targets, and suggested potential therapeutic applications. Integration of phosphoproteomic data refined drug-affected pathways, identified response markers, and strengthened rationale for combination treatments. We exemplify translational value by discovering SIK2 (salt-inducible kinase 2) inhibitors that modulate cytokine production in primary cells, by identifying drugs against the lung cancer survival marker MELK (maternal embryonic leucine zipper kinase), and by repurposing cabozantinib to treat FLT3-ITD-positive acute myeloid leukemia. This resource, available via the ProteomicsDB database, should facilitate basic, clinical, and drug discovery research and aid clinical decision-making. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000416584000032 |
WOS关键词 | INTEGRATIVE GENOMICS VIEWER ; SALT-INDUCIBLE KINASES ; CHEMICAL PROTEOMICS ; INHIBITOR SELECTIVITY ; COMPREHENSIVE ANALYSIS ; DATA QUALITY ; PROTEIN ; QUANTIFICATION ; REFINEMENT ; CANCER |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/197448 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.TUM, Chair Prote & Bioanalyt, Freising Weihenstephan, Germany; 2.German Canc Consortium DKTK, Heidelberg, Germany; 3.German Canc Res Ctr, Heidelberg, Germany; 4.Ludwig Maximilians Univ LMU Munchen, Univ Hosp, Dept Internal Med 3, Munich, Germany; 5.German Ctr Environm Hlth HMGU, Helmholtz Ctr Munich, Dept Apoptosis Hematopoiet Stem Cells, Munich, Germany; 6.TUM, Inst Klin Chem & Pathobiochem, Munich, Germany; 7.Nerviano Med Sci Srl, Oncol, Milan, Italy; 8.Helmholtz Zentrum Munchen, Res Unit Analyt Pathol, Neuherberg, Germany; 9.SAP SE, Potsdam, Germany; 10.TUM, Klinikum Rechts Isar, Dept Med 3, Munich, Germany; 11.Charite, Struct Bioinformat Grp, Berlin, Germany; 12.Univ Freiburg, Univ Med Ctr Freiburg, Inst Surg Pathol, Fac Med, Freiburg, Germany; 13.Ctr Thorac Surg, Krefeld, Germany; 14.Univ Tartu, Estonian Genome Ctr, Tartu, Estonia; 15.Tartu Univ Hosp, Tartu, Estonia; 16.SAP SE, Walldorf, Germany; 17.TUM, Dept Chem, Garching, Germany; 18.CIPSM, Munich, Germany; 19.LMU, Dr von Hauner Childrens Hosp, Dept Pediat, Munich, Germany; 20.TUM, Bavarian Biomol Mass Spectrometry Ctr BayBioMS, Freising Weihenstephan, Germany |
推荐引用方式 GB/T 7714 | Klaeger, Susan,Heinzlmeir, Stephanie,Wilhelm, Mathias,et al. The target landscape of clinical kinase drugs[J]. SCIENCE,2017,358(6367). |
APA | Klaeger, Susan.,Heinzlmeir, Stephanie.,Wilhelm, Mathias.,Polzer, Harald.,Vick, Binje.,...&Kuster, Bernhard.(2017).The target landscape of clinical kinase drugs.SCIENCE,358(6367). |
MLA | Klaeger, Susan,et al."The target landscape of clinical kinase drugs".SCIENCE 358.6367(2017). |
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