• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利:CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法,用中文像聊天一样搜索,搜遍4000万医学文献。AI智能推荐,让科研检索更轻松。

立即免费搜索

文件翻译

保留排版,准确专业,支持PDF/Word/PPT等文件格式,支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述,25分钟生成高质量综述,智能提取关键信息,辅助科研写作。

立即免费体验

外成系统药理学将创新的计算方法与高通量全脊椎动物研究相结合。

Outside-In Systems Pharmacology Combines Innovative Computational Methods With High-Throughput Whole Vertebrate Studies.

机构信息

Systems Biomedicine and Pharmacology, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands.

DMPK, Oncology, Innovative Medicines and Early Development, AstraZeneca, Chesterford Research Park, UK.

出版信息

CPT Pharmacometrics Syst Pharmacol. 2018 May;7(5):285-287. doi: 10.1002/psp4.12297. Epub 2018 Apr 25.

DOI:10.1002/psp4.12297
PMID:29693322
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5980533/
Abstract

To advance the systems approach in pharmacology, experimental models and computational methods need to be integrated from early drug discovery onward. Here, we propose outside-in model development, a model identification technique to understand and predict the dynamics of a system without requiring prior biological and/or pharmacological knowledge. The advanced data required could be obtained by whole vertebrate, high-throughput, low-resource dose-exposure-effect experimentation with the zebrafish larva. Combinations of these innovative techniques could improve early drug discovery.

摘要

为了推进药理学中的系统方法,需要从早期药物发现开始整合实验模型和计算方法。在这里,我们提出了一种从外向内的模型开发方法,这是一种模型识别技术,可以在不要求事先具备生物学和/或药理学知识的情况下理解和预测系统的动态。所需的先进数据可以通过使用斑马鱼幼虫进行全脊椎动物、高通量、低资源剂量-暴露-效应实验来获得。这些创新技术的结合可以提高早期药物发现的效率。

相似文献

1
Outside-In Systems Pharmacology Combines Innovative Computational Methods With High-Throughput Whole Vertebrate Studies.外成系统药理学将创新的计算方法与高通量全脊椎动物研究相结合。
CPT Pharmacometrics Syst Pharmacol. 2018 May;7(5):285-287. doi: 10.1002/psp4.12297. Epub 2018 Apr 25.
2
Systems pharmacology for drug discovery and development: paradigm shift or flash in the pan?系统药理学在药物发现和开发中的应用:范式转变还是昙花一现?
Clin Pharmacol Ther. 2013 May;93(5):379-81. doi: 10.1038/clpt.2013.40.
3
Recent progress in the use of zebrafish for novel cardiac drug discovery.斑马鱼在新型心脏药物发现中的应用最新进展。
Expert Opin Drug Discov. 2015;10(11):1231-41. doi: 10.1517/17460441.2015.1078788. Epub 2015 Aug 18.
4
Relevance of systems pharmacology in drug discovery.系统药理学在药物发现中的相关性。
Drug Discov Today. 2012 Jul;17(13-14):665-70. doi: 10.1016/j.drudis.2012.01.015. Epub 2012 Jan 25.
5
Biocomputational resources useful for drug discovery against compartmentalized targets.针对分隔靶点的药物发现有用的生物计算资源。
Curr Pharm Des. 2014;20(2):293-300. doi: 10.2174/13816128113199990030.
6
Integration not isolation: arguing the case for quantitative and systems pharmacology in drug discovery and development.整合而非孤立:为药物发现和开发中的定量和系统药理学辩护。
Drug Discov Today. 2011 Dec;16(23-24):1031-6. doi: 10.1016/j.drudis.2011.10.001. Epub 2011 Oct 13.
7
Systems Pharmacology in Small Molecular Drug Discovery.系统药理学在小分子药物发现中的应用。
Int J Mol Sci. 2016 Feb 18;17(2):246. doi: 10.3390/ijms17020246.
8
Network-based technologies for early drug discovery.基于网络的早期药物发现技术。
Drug Discov Today. 2018 Mar;23(3):626-635. doi: 10.1016/j.drudis.2017.12.001. Epub 2017 Dec 30.
9
Systems pharmacology to predict drug toxicity: integration across levels of biological organization.系统药理学预测药物毒性:跨越生物学组织层次的整合。
Annu Rev Pharmacol Toxicol. 2013;53:451-73. doi: 10.1146/annurev-pharmtox-011112-140248. Epub 2012 Nov 5.
10
Quantitative Systems Pharmacology: A Case for Disease Models.定量系统药理学:疾病模型的一个实例
Clin Pharmacol Ther. 2017 Jan;101(1):24-27. doi: 10.1002/cpt.528. Epub 2016 Nov 18.

引用本文的文献

1
An anti-tuberculosis compound screen using a zebrafish infection model identifies an aspartyl-tRNA synthetase inhibitor.利用斑马鱼感染模型进行抗结核化合物筛选,鉴定出一种天冬氨酰-tRNA 合成酶抑制剂。
Dis Model Mech. 2021 Dec 1;14(12). doi: 10.1242/dmm.049145. Epub 2021 Dec 23.
2
Zebrafish larvae as experimental model to expedite the search for new biomarkers and treatments for neonatal sepsis.斑马鱼幼体作为加速寻找新生儿败血症新生物标志物和治疗方法的实验模型。
J Clin Transl Sci. 2021 Jun 18;5(1):e140. doi: 10.1017/cts.2021.803. eCollection 2021.
3
Drug Resistance in Nontuberculous Mycobacteria: Mechanisms and Models.

本文引用的文献

1
Frequency-Domain Response Analysis for Quantitative Systems Pharmacology Models.定量系统药理学模型的频域响应分析
CPT Pharmacometrics Syst Pharmacol. 2017 Nov 28;7(2):111-23. doi: 10.1002/psp4.12266.
2
Opportunities and challenges in phenotypic drug discovery: an industry perspective.表型药物发现的机遇与挑战:行业视角。
Nat Rev Drug Discov. 2017 Aug;16(8):531-543. doi: 10.1038/nrd.2017.111. Epub 2017 Jul 7.
3
The Zebrafish Model Organism Database: new support for human disease models, mutation details, gene expression phenotypes and searching.
非结核分枝杆菌中的耐药性:机制与模型
Biology (Basel). 2021 Jan 29;10(2):96. doi: 10.3390/biology10020096.
4
Anti-tuberculosis effect of isoniazid scales accurately from zebrafish to humans.异烟肼的抗结核作用在从斑马鱼到人类的范围内都能得到准确衡量。
Br J Pharmacol. 2020 Dec;177(24):5518-5533. doi: 10.1111/bph.15247. Epub 2020 Nov 3.
5
Quantification of Natural Growth of Two Strains of Mycobacterium Marinum for Translational Antituberculosis Drug Development.两种海洋分枝杆菌天然生长的定量研究 为抗结核药物转化开发。
Clin Transl Sci. 2020 Nov;13(6):1060-1064. doi: 10.1111/cts.12793. Epub 2020 May 10.
6
Optimization of Cancer Treatment in the Frequency Domain.在频域优化癌症治疗。
AAPS J. 2019 Sep 11;21(6):106. doi: 10.1208/s12248-019-0372-4.
7
Impact of post-hatching maturation on the pharmacokinetics of paracetamol in zebrafish larvae.孵化后成熟对斑马鱼幼鱼中扑热息痛药代动力学的影响。
Sci Rep. 2019 Feb 15;9(1):2149. doi: 10.1038/s41598-019-38530-w.
8
Pharmacometrics and/or Systems Pharmacology.药物计量学和/或系统药理学
CPT Pharmacometrics Syst Pharmacol. 2019 Jun;8(6):331-332. doi: 10.1002/psp4.12376. Epub 2019 Feb 2.
斑马鱼模式生物数据库:为人类疾病模型、突变细节、基因表达表型及搜索提供新支持。
Nucleic Acids Res. 2017 Jan 4;45(D1):D758-D768. doi: 10.1093/nar/gkw1116. Epub 2016 Nov 28.
4
Pharmacokinetic Modeling of Paracetamol Uptake and Clearance in Zebrafish Larvae: Expanding the Allometric Scale in Vertebrates with Five Orders of Magnitude.对乙酰氨基酚在斑马鱼幼体中的吸收和清除的药代动力学建模:在五个数量级上扩展脊椎动物的异速生长尺度
Zebrafish. 2016 Dec;13(6):504-510. doi: 10.1089/zeb.2016.1313. Epub 2016 Sep 15.
5
Systems pharmacology - Towards the modeling of network interactions.系统药理学——迈向网络相互作用建模
Eur J Pharm Sci. 2016 Oct 30;94:4-14. doi: 10.1016/j.ejps.2016.04.027. Epub 2016 Apr 27.
6
Cybernetics, Redux: An Outside-In Strategy for Unraveling Cellular Function.控制论,再探:一种从外向内解析细胞功能的策略。
Dev Cell. 2016 Jan 11;36(1):2-4. doi: 10.1016/j.devcel.2015.12.025.
7
Establishment and optimization of a high throughput setup to study Staphylococcus epidermidis and Mycobacterium marinum infection as a model for drug discovery.建立并优化一种高通量实验装置,以研究表皮葡萄球菌和海分枝杆菌感染,作为药物研发的模型。
J Vis Exp. 2014 Jun 26(88):e51649. doi: 10.3791/51649.
8
The frequency dependence of osmo-adaptation in Saccharomyces cerevisiae.酿酒酵母中渗透适应的频率依赖性。
Science. 2008 Jan 25;319(5862):482-4. doi: 10.1126/science.1151582.