激酶药物再利用和靶点发现的新机遇。
New opportunities for kinase drug repurposing and target discovery.
机构信息
Institute for Pharmaceutical Chemistry, Johann Wolfgang Goethe-University, Max-von-Laue-Str. 9, Frankfurt, D-60438, Germany.
Structural Genomics Consortium, Buchmann Institute for Molecular Life Sciences, Johann Wolfgang Goethe-University, Max-von-Laue-Str. 15, Frankfurt, D-60438, Germany.
出版信息
Br J Cancer. 2018 Apr;118(7):936-937. doi: 10.1038/s41416-018-0045-6. Epub 2018 Mar 16.
Abstract
Protein kinases are major drug targets for oncology. The large size of the kinome, active site conservation and the influence of activation states on drug binding complicates the analysis of their cellular mode of action. In a recent article in Science, Klaeger et al. analysed cellular targets of 243 drug candidates providing a large repository of data for drug repurposing.
摘要
蛋白激酶是肿瘤学的主要药物靶点。激酶组的庞大规模、活性位点的保守性以及激活状态对药物结合的影响，使得分析其细胞作用模式变得复杂。在最近的《科学》杂志的一篇文章中，Klaeger 等人分析了 243 种候选药物的细胞靶标，为药物再利用提供了大量数据存储库。
相似文献
1
New opportunities for kinase drug repurposing and target discovery.激酶药物再利用和靶点发现的新机遇。
Br J Cancer. 2018 Apr;118(7):936-937. doi: 10.1038/s41416-018-0045-6. Epub 2018 Mar 16.
2
Repurposing existing therapeutics, its importance in oncology drug development: Kinases as a potential target.重新利用现有疗法，其在肿瘤药物开发中的重要性：激酶作为一个潜在的靶点。
Br J Clin Pharmacol. 2022 Jan;88(1):64-74. doi: 10.1111/bcp.14964. Epub 2021 Jul 9.
3
Large-scale detection of drug off-targets: hypotheses for drug repurposing and understanding side-effects.药物脱靶的大规模检测：药物重新利用及理解副作用的假说
BMC Pharmacol Toxicol. 2017 Apr 28;18(1):18. doi: 10.1186/s40360-017-0128-7.
4
Drug-repositioning opportunities for cancer therapy: novel molecular targets for known compounds.癌症治疗的药物再定位机会：已知化合物的新型分子靶标。
Drug Discov Today. 2016 Jan;21(1):190-199. doi: 10.1016/j.drudis.2015.09.017. Epub 2015 Oct 9.
5
In silico drug repositioning: what we need to know.计算机药物重定位：我们需要了解的内容。
Drug Discov Today. 2013 Feb;18(3-4):110-5. doi: 10.1016/j.drudis.2012.08.005. Epub 2012 Aug 28.
6
Identify drug repurposing candidates by mining the protein data bank.通过挖掘蛋白质数据库来识别药物再利用候选物。
Brief Bioinform. 2011 Jul;12(4):336-40. doi: 10.1093/bib/bbr017. Epub 2011 Apr 21.
7
K-Map: connecting kinases with therapeutics for drug repurposing and development.K-Map：将激酶与治疗药物联系起来，用于药物重定位和开发。
Hum Genomics. 2013 Sep 23;7(1):20. doi: 10.1186/1479-7364-7-20.
8
Computational Drug Repurposing: Current Trends.计算药物再利用：现状趋势。
Curr Med Chem. 2019;26(28):5389-5409. doi: 10.2174/0929867325666180530100332.
9
Literature-based discovery of new candidates for drug repurposing.基于文献的药物重新利用新候选物发现。
Brief Bioinform. 2017 May 1;18(3):488-497. doi: 10.1093/bib/bbw030.
10
The drug repurposing landscape from 2012 to 2017: evolution, challenges, and possible solutions.2012 年至 2017 年的药物再利用领域：演变、挑战及可能的解决方案。
Drug Discov Today. 2019 Mar;24(3):789-795. doi: 10.1016/j.drudis.2018.11.022. Epub 2018 Dec 1.
引用本文的文献
1
Computational Development of Allosteric Peptide Inhibitors Targeting LIM Kinases as a Novel Therapeutic Intervention.靶向LIM激酶的变构肽抑制剂的计算开发作为一种新型治疗干预手段
Cell Biochem Biophys. 2025 Mar 18. doi: 10.1007/s12013-025-01718-1.
2
A comprehensive exploration of the druggable conformational space of protein kinases using AI-predicted structures.利用人工智能预测结构全面探索蛋白激酶的可成药性构象空间。
PLoS Comput Biol. 2024 Jul 24;20(7):e1012302. doi: 10.1371/journal.pcbi.1012302. eCollection 2024 Jul.
3
TBK1, a prioritized drug repurposing target for amyotrophic lateral sclerosis: evidence from druggable genome Mendelian randomization and pharmacological verification in vitro.TBK1 是肌萎缩侧索硬化症的优先药物重定位靶点：来自可用药基因组 Mendelian 随机化和体外药理学验证的证据。
BMC Med. 2024 Mar 5;22(1):96. doi: 10.1186/s12916-024-03314-1.
4
Current trends and future prospects of drug repositioning in gastrointestinal oncology.胃肠道肿瘤药物重新定位的当前趋势与未来前景
Front Pharmacol. 2024 Jan 4;14:1329244. doi: 10.3389/fphar.2023.1329244. eCollection 2023.
5
Anti-Leukaemic Activity of Rilpivirine Is Mediated by Aurora A Kinase Inhibition.利匹韦林的抗白血病活性由极光激酶A抑制介导。
Cancers (Basel). 2023 Feb 7;15(4):1044. doi: 10.3390/cancers15041044.
6
Combined and Evidence Supporting an Aurora A Kinase Inhibitory Role of the Anti-Viral Drug Rilpivirine and an Anti-Proliferative Influence on Cancer Cells.联合证据支持抗病毒药物利匹韦林的极光激酶A抑制作用及对癌细胞的抗增殖影响。
Pharmaceuticals (Basel). 2022 Sep 25;15(10):1186. doi: 10.3390/ph15101186.
7
Targeting Protein Kinases and Epigenetic Control as Combinatorial Therapy Options for Advanced Prostate Cancer Treatment.靶向蛋白激酶和表观遗传调控作为晚期前列腺癌治疗的联合治疗选择
Pharmaceutics. 2022 Feb 25;14(3):515. doi: 10.3390/pharmaceutics14030515.
8
Exploring the Conformational Landscape and Stability of Aurora A Using Ion-Mobility Mass Spectrometry and Molecular Modeling.利用离子淌度质谱和分子建模技术探索 Aurora A 的构象景观和稳定性。
J Am Soc Mass Spectrom. 2022 Mar 2;33(3):420-435. doi: 10.1021/jasms.1c00271. Epub 2022 Jan 31.
9
Computational modeling identifies multitargeted kinase inhibitors as effective therapies for metastatic, castration-resistant prostate cancer.计算模型确定多靶点激酶抑制剂是转移性去势抵抗性前列腺癌的有效治疗方法。
Proc Natl Acad Sci U S A. 2021 Oct 5;118(40). doi: 10.1073/pnas.2103623118. Epub 2021 Sep 30.
10
Characterising proteolysis during SARS-CoV-2 infection identifies viral cleavage sites and cellular targets with therapeutic potential.阐明 SARS-CoV-2 感染过程中的蛋白水解作用可鉴定具有治疗潜力的病毒裂解位点和细胞靶标。
Nat Commun. 2021 Sep 21;12(1):5553. doi: 10.1038/s41467-021-25796-w.
本文引用的文献
1
The target landscape of clinical kinase drugs.临床激酶药物的目标格局。
Science. 2017 Dec 1;358(6367). doi: 10.1126/science.aan4368.
2
Quantitative, Wide-Spectrum Kinase Profiling in Live Cells for Assessing the Effect of Cellular ATP on Target Engagement.在活细胞中进行定量、广谱激酶分析，以评估细胞 ATP 对靶标结合的影响。
Cell Chem Biol. 2018 Feb 15;25(2):206-214.e11. doi: 10.1016/j.chembiol.2017.10.010. Epub 2017 Nov 22.
3
Comprehensive characterization of the Published Kinase Inhibitor Set.全面表征已发表的激酶抑制剂集。
Nat Biotechnol. 2016 Jan;34(1):95-103. doi: 10.1038/nbt.3374. Epub 2015 Oct 26.
4
Optimized chemical proteomics assay for kinase inhibitor profiling.用于激酶抑制剂分析的优化化学蛋白质组学检测方法。
J Proteome Res. 2015 Mar 6;14(3):1574-86. doi: 10.1021/pr5012608. Epub 2015 Feb 20.
5
Ten things you should know about protein kinases: IUPHAR Review 14.关于蛋白激酶你应该了解的十件事：IUPHAR综述14
Br J Pharmacol. 2015 Jun;172(11):2675-700. doi: 10.1111/bph.13096. Epub 2015 Mar 24.
6
Dual kinase-bromodomain inhibitors for rationally designed polypharmacology.双激酶-溴结构域抑制剂用于合理设计的多药理学。
Nat Chem Biol. 2014 Apr;10(4):305-12. doi: 10.1038/nchembio.1471. Epub 2014 Mar 2.
7
Network-based approach identified cell cycle genes as predictor of overall survival in lung adenocarcinoma patients.基于网络的方法鉴定出细胞周期基因作为肺腺癌患者总生存期的预测因子。
Lung Cancer. 2013 Apr;80(1):91-8. doi: 10.1016/j.lungcan.2012.12.022. Epub 2013 Jan 26.
8
Cabozantinib (XL184), a novel MET and VEGFR2 inhibitor, simultaneously suppresses metastasis, angiogenesis, and tumor growth.卡博替尼（XL184），一种新型的 MET 和 VEGFR2 抑制剂，可同时抑制转移、血管生成和肿瘤生长。
Mol Cancer Ther. 2011 Dec;10(12):2298-308. doi: 10.1158/1535-7163.MCT-11-0264. Epub 2011 Sep 16.
9
A quantitative analysis of kinase inhibitor selectivity.激酶抑制剂选择性的定量分析。
Nat Biotechnol. 2008 Jan;26(1):127-32. doi: 10.1038/nbt1358.
10
A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases.已验证的激酶抑制剂与丝氨酸/苏氨酸激酶的系统性相互作用图谱。
Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20523-8. doi: 10.1073/pnas.0708800104. Epub 2007 Dec 11.
Zotero 插件