Suppr超能文献

多药理学与药物发现的系统方法。

Systems approaches to polypharmacology and drug discovery.

作者信息

Boran Aislyn D W, Iyengar Ravi

机构信息

Mount Sinai School of Medicine, Department of Pharmacology and Systems Therapeutics, One Gustave L Levy Place, New York, NY 10029, USA.

出版信息

Curr Opin Drug Discov Devel. 2010 May;13(3):297-309.

Abstract

Systems biology uses experimental and computational approaches to characterize large sample populations systematically, process large datasets, examine and analyze regulatory networks, and model reactions to determine how components are joined to form functional systems. Systems biology technologies, data and knowledge are particularly useful in understanding disease processes and drug actions. An important area of integration between systems biology and drug discovery is the concept of polypharmacology: the treatment of diseases by modulating more than one target. Polypharmacology for complex diseases is likely to involve multiple drugs acting on distinct targets that are part of a network regulating physiological responses. This review discusses the current state of the systems-level understanding of diseases and both the therapeutic and adverse mechanisms of drug actions. Drug-target networks can be used to identify multiple targets and to determine suitable combinations of drug targets or drugs. Thus, the discovery of new drug therapies for complex diseases may be greatly aided by systems biology.

摘要

系统生物学采用实验和计算方法来系统地表征大样本群体,处理大型数据集,检查和分析调控网络,并对反应进行建模,以确定各组成部分如何结合形成功能系统。系统生物学技术、数据和知识在理解疾病过程和药物作用方面特别有用。系统生物学与药物发现之间整合的一个重要领域是多药理学概念:通过调节多个靶点来治疗疾病。针对复杂疾病的多药理学可能涉及作用于不同靶点的多种药物,这些靶点是调节生理反应的网络的一部分。本综述讨论了疾病系统层面理解的现状以及药物作用的治疗和不良反应机制。药物 - 靶点网络可用于识别多个靶点,并确定药物靶点或药物的合适组合。因此,系统生物学可能极大地有助于发现针对复杂疾病的新药物疗法。

相似文献

1
Systems approaches to polypharmacology and drug discovery.
Curr Opin Drug Discov Devel. 2010 May;13(3):297-309.
2
Using quantitative systems pharmacology for novel drug discovery.
Expert Opin Drug Discov. 2015 Dec;10(12):1315-31. doi: 10.1517/17460441.2015.1082543. Epub 2015 Aug 25.
3
Transcriptome inference and systems approaches to polypharmacology and drug discovery in herbal medicine.
J Ethnopharmacol. 2017 Jan 4;195:127-136. doi: 10.1016/j.jep.2016.10.020. Epub 2016 Nov 25.
4
In Silico Oncology Drug Repositioning and Polypharmacology.
Methods Mol Biol. 2019;1878:243-261. doi: 10.1007/978-1-4939-8868-6_15.
5
Systems pharmacology: network analysis to identify multiscale mechanisms of drug action.
Annu Rev Pharmacol Toxicol. 2012;52:505-21. doi: 10.1146/annurev-pharmtox-010611-134520.
6
Harnessing Polypharmacology with Computer-Aided Drug Design and Systems Biology.
Curr Pharm Des. 2016;22(21):3097-108. doi: 10.2174/1381612822666160224141930.
7
Improving the efficacy-safety balance of polypharmacology in multi-target drug discovery.
Expert Opin Drug Discov. 2018 Feb;13(2):179-192. doi: 10.1080/17460441.2018.1413089. Epub 2017 Dec 12.
8
Network analyses in systems pharmacology.
Bioinformatics. 2009 Oct 1;25(19):2466-72. doi: 10.1093/bioinformatics/btp465. Epub 2009 Jul 30.
9
Recent Advances in the System Biology-based Target Identification and Drug Discovery.
Curr Top Med Chem. 2018;18(20):1737-1744. doi: 10.2174/1568026618666181025112344.
10
Network-based drug discovery by integrating systems biology and computational technologies.
Brief Bioinform. 2013 Jul;14(4):491-505. doi: 10.1093/bib/bbs043. Epub 2012 Aug 9.

引用本文的文献

1
Multiscale analysis and optimal glioma therapeutic candidate discovery using the CANDO platform.
bioRxiv. 2025 May 23:2025.05.19.654757. doi: 10.1101/2025.05.19.654757.
6
Recent updates on potential of VEGFR-2 small-molecule inhibitors as anticancer agents.
RSC Adv. 2024 Oct 22;14(45):33384-33417. doi: 10.1039/d4ra05244g. eCollection 2024 Oct 17.
9
Convenient synthesis and X-ray determination of 2-amino-6-1,3,4-thiadiazin-3-ium bromides endowed with antiproliferative activity.
RSC Adv. 2024 Jun 27;14(25):17866-17876. doi: 10.1039/d4ra02531h. eCollection 2024 May 28.
10
De novo generation of multi-target compounds using deep generative chemistry.
Nat Commun. 2024 May 6;15(1):3636. doi: 10.1038/s41467-024-47120-y.

本文引用的文献

1
Recent advances in the research and development of B-Raf inhibitors.
Curr Med Chem. 2010;17(16):1618-34. doi: 10.2174/092986710791111242.
2
Kinase-dead BRAF and oncogenic RAS cooperate to drive tumor progression through CRAF.
Cell. 2010 Jan 22;140(2):209-21. doi: 10.1016/j.cell.2009.12.040.
3
RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth.
Nature. 2010 Mar 18;464(7287):431-5. doi: 10.1038/nature08833. Epub 2010 Feb 3.
4
The PI3K pathway as drug target in human cancer.
J Clin Oncol. 2010 Feb 20;28(6):1075-83. doi: 10.1200/JCO.2009.25.3641. Epub 2010 Jan 19.
5
Matchmaking service links up researchers to wallflower drugs.
Nat Med. 2010 Jan;16(1):7. doi: 10.1038/nm0110-7b.
6
Beta-lactam antibiotics: from antibiosis to resistance and bacteriology.
APMIS. 2010 Jan;118(1):1-36. doi: 10.1111/j.1600-0463.2009.02563.x.
8
Update of TTD: Therapeutic Target Database.
Nucleic Acids Res. 2010 Jan;38(Database issue):D787-91. doi: 10.1093/nar/gkp1014. Epub 2009 Nov 20.
9
Direct inhibition of the NOTCH transcription factor complex.
Nature. 2009 Nov 12;462(7270):182-8. doi: 10.1038/nature08543.
10
Edgetic perturbation models of human inherited disorders.
Mol Syst Biol. 2009;5:321. doi: 10.1038/msb.2009.80. Epub 2009 Nov 3.

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验