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1.
高内涵药物筛选已经成为药物发现领域的一个重要部分,在生物医药领域里的重要性日益突显,其广泛应用必然会为药物发现带来新的希望与突破。高内涵药物筛选方法具有许多独特的优势,它使得药物筛选更趋生物化。本文介绍了高内涵药物筛选的发展过程,及其当前和潜在的应用领域,探讨了高内涵药物筛选与其他研发技术手段之间的关系,并就其在新药发现中的作用和前景进行了阐述。  相似文献   

2.
化合物药物活性的高通量筛选   总被引:12,自引:2,他引:10  
介绍高通量药物筛选系统的组成及其相关技术。结合国家药物筛选中心的工作,详细介绍了化合物药物活性的高通量筛选的4 个组成部分及其在药物发现过程中的作用。高通量药物筛选系统是一个涉及多个学科的、以分子生物学、新型检测技术技术为基础的新型药物发现系统。高通量药物筛选系统的顺利开展可以加速我国的新药研究  相似文献   

3.
国家新药筛选中心暨依托单位中科院上海药物研究所最近与美国Cellomics公司签署战略合作协议,共同建设具有世界先进水平的高内涵药物筛选技术平台。这一项目的启动标志着我国创新药物的研究策略和技术手段进入了一个崭新的发展阶段,对于在创新药物研究中应用系统生物学思想,建立基因组时代的药物研究新模式都具有重要意义。  相似文献   

4.
高内涵药物筛选方法的研究及应用   总被引:7,自引:0,他引:7  
张莉  杜冠华 《药学学报》2005,40(6):486-490
高通量药物筛选 (high throughputscreening,HTS)是 20世纪 80年代中期产生的为寻找先导物针对大量样品进行药理活性评价分析的一种技术手段,在创新药物的研究和开发中发挥了重要作用。本室于 1998年在国内率先将其用于创新药物的研究,已发现一批具有潜在研究价值的化合物 [1, 2]。近年来在药物发现领域又出现了一个新概念———高内涵药物筛选 (high contentscreening,HCS)。本文就高内涵药物筛选目前的研究和应用情况作一讨论。1 高通量药物筛选与高内涵药物筛选高通量药物筛选是以药物发现的基本规律为基础,应用药理学、生物化学…  相似文献   

5.
梁婷  焦强  陆涛 《药学进展》2011,35(4):162-168
概述现代药物筛选方法和新一代分布式计算技术,重点介绍云计算和网格计算技术在药物筛选中的应用,并讨论这些技术在应用过程中存在的问题。药物筛选旨在从大量化合物中发现有活性的化合物,是发现先导化合物和新药的重要途径。药物筛选中数据管理和分析结果为新药研发中先导化合物的发现提供了重要依据。利用新一代分布式计算技术管理和分析实验数据可大大提高效率,降低研发成本、缩短研发周期。  相似文献   

6.
高通量筛选与药物创新   总被引:1,自引:0,他引:1  
王瑜  李鹏  齐帜 《上海医药》2004,25(2):67-69
药物研究是关系人类健康的事业,开发新药可以产生巨大的经济和社会效益,创新药物的研究和开发已经成为医药领域长期的重要课题。新药研究不仅需要依赖坚实的基础研究成果,其自身也具有独特的规律和要求,掌握这些规律和要求,有助于促进创新药物的发现和研究。本文根据相关文献,讨论了创新药物的类型和特点,在此基础上论述了创新药物研究的理论和高通量药物筛选在创新药物研究中的应用。  相似文献   

7.
创新药物研究与高通量筛选   总被引:7,自引:1,他引:6  
根据新药研究的资料,讨论了创新药物的特点和开发研究的规律。总结了创新药物的类型,论述了创新药物的发现,研究的关键技术问题和思路,根据实际工作内容,介绍了高通量药物筛选的概念、原理、方法和步骤,分析了高通量药物筛选技术在创新药物研究中的优势和不足,论述了高通量药物筛选技术在创新药物研究中的地位和应用前景。  相似文献   

8.
药物研究是关系人类健康的事业,开发新药可以产生巨大的经济和社会效益,创新药物的研究和开发已经成为医药领域长期的重要课题。新药研究不仅需要依赖坚实的基础研究成果,其自身也具有独特的规律和要求,掌握这些规律和要求,有助于促进创新药物的发现和研究。笔者根据相关文献,讨论了创新药物的类型和特点,在此基础上论述了创新药物研究的理论和高通量药物筛选在创新药物研究中的应用。  相似文献   

9.
毒性已成为新药开发过程中淘汰的主要原因。近年来制药和生物技术工业的研究人员开发了多种新技术以便在药物发现和开发过程中尽早确定化合物的安全特性。笔者首先对药物毒性产生的原因如药靶的特异性、药物的分子结构、药物代谢和代谢动力学等方面进行了分析,再介绍了近几年早期毒性筛选的新技术,包括预测模型、体外高通量毒性筛选、活性代谢产物的检测、高内涵筛选技术、动物实验。  相似文献   

10.
创新药物研究与高通量筛选   总被引:4,自引:0,他引:4  
根据新药研究的资料,讨论了创新药物的特点和开发研究的规律,总结了创新药物的类型,论述了创新药物的发现、研究的关键技术问题和思路.根据实际工作内容,介绍了高通量药物筛选的概念、原理、方法和步骤,分析了高通量药物筛选技术在创新药物研究中的优势和不足,论述了高通量药物筛选技术在创新药物研究中的地位和应用前景.  相似文献   

11.
Importance of the field: Miniaturization is the key to advancing the state of the art in high-content screening (HCS) in order to enable dramatic cost savings through reduced usage of expensive biochemical reagents and to enable large-scale screening on primary cells. Microfluidic technology offers the potential to enable HCS to be performed with an unprecedented degree of miniaturization.

Areas covered in this review: This perspective highlights a real-world example from the authors' work of HCS assays implemented in a highly miniaturized microfluidic format. The advantages of this technology are discussed, including cost savings, high-throughput screening on primary cells, improved accuracy, the ability to study complex time-varying stimuli, and ease of automation, integration and scaling.

What the reader will gain: The reader will understand the capabilities of a new microfluidics-based platform for HCS and the advantages it provides over conventional plate-based HCS.

Take home message: Microfluidics technology will drive significant advancements and broader usage and applicability of HCS in drug discovery.  相似文献   

12.
ABSTRACT

Introduction: High-content screening (HCS) was introduced about twenty years ago as a promising analytical approach to facilitate some critical aspects of drug discovery. Its application has spread progressively within the pharmaceutical industry and academia to the point that it today represents a fundamental tool in supporting drug discovery and development.

Areas covered: Here, the authors review some of significant progress in the HCS field in terms of biological models and assay readouts. They highlight the importance of high-content screening in drug discovery, as testified by its numerous applications in a variety of therapeutic areas: oncology, infective diseases, cardiovascular and neurodegenerative diseases. They also dissect the role of HCS technology in different phases of the drug discovery pipeline: target identification, primary compound screening, secondary assays, mechanism of action studies and in vitro toxicology.

Expert opinion: Recent advances in cellular assay technologies, such as the introduction of three-dimensional (3D) cultures, induced pluripotent stem cells (iPSCs) and genome editing technologies (e.g., CRISPR/Cas9), have tremendously expanded the potential of high-content assays to contribute to the drug discovery process. Increasingly predictive cellular models and readouts, together with the development of more sophisticated and affordable HCS readers, will further consolidate the role of HCS technology in drug discovery.  相似文献   

13.
Introduction: The need for alternatives to animal experimentation and traditional testing methods has been widely discussed in recent years. This has led scientists and regulatory authorities to investigate alternative methods for toxicity testing. High-content screening (HCS) has emerged as a powerful tool in predictive toxicology since it permits molecular, cellular and tissue-based toxicity assessments. HCS allows automated image acquisition and analysis, and provides information on multiple properties of individual cells loaded simultaneously with fluorescent dyes, which is used for drug safety evaluations.

Areas covered: Herein, the authors review the principles of HCS technology and some of the most widely used HCS assays for studying drug-induced hepatotoxicity in preclinical studies in general and in the pharmaceutical industry in particular.

Expert opinion: The widespread acceptation of HCS by pharmaceutical companies and academic researchers highlights the potential usefulness of this technology as a prioritization tool in drug development. The improvement of different key points such as fluorescent probes or bioinformatics tools will consolidate HCS in drug discovery.  相似文献   

14.
Background: High-content screening (HCS) defines a series of cell-based multiparametric approaches for analysis at the single-cell level. In recent years, HCS has been increasingly pursued in the drug discovery field, adding to the repertoire of assay type, or increasing throughput in applications such as compound screening and mechanism of action studies, as well as for target identification/validation (siRNA screening). Obviously, as cells represent the objects of high-content assays, the outcome of any HCS assay is determined by the cell type: the choice of the most suitable cellular model for a given assay is a critical step that must follow biological and technical criteria. Method: Here, I discuss these criteria and report a systematic survey of cell types used so far in HCS, with particular emphasis on their strengths and drawbacks. I also illustrate my expectations for future advances on cellular models used in HCS. Conclusion: Despite the plethora of cell types potentially suitable for HCS, so far only a handful of cellular models (particularly human cancer cell lines) account for the great majority of HCS assays. In the future, the introduction of novel cell types, including engineered and primary cells, will further expand the potential of HCS for systems biology and drug discovery.  相似文献   

15.
高通量筛选药动学模型的研究进展   总被引:2,自引:0,他引:2  
高通量筛选体系在创新药物药动学筛选中的应用是当前新药开发研究的一个重要领域。建立合理的药动学筛选模型不仅可以降低新药开发的成本,并且可以在新药研究早期对其作出正确的评价。本文对当前常用的高通量筛选药动学模型作了简单的回顾,指出了合理的药动学筛选模型在寻找新药过程中的重要性,以及建立药动学筛选模型的紧迫性。  相似文献   

16.
Background: Computational support for high-content screening (HCS) is of paramount importance at several stages of the process: from the selection of compounds, to the image and data analysis all the way to hit identification and analysis of mechanisms of action. Method: Here, we describe computational approaches to improve the benefit gained from HCS, such as compound selection, image analysis and algorithms to further process and explore HCS data. We describe the current challenges in these areas and state our expectations for the field. Conclusion: At present there are no standard approaches for correction, normalization, analysis or visualization of HCS data. Thus, the information-rich data sets provided by HCS are exploited to only a limited extent. To overcome this shortcoming, a thorough comparison and evaluation of different tools is needed.  相似文献   

17.
Importance of the field: Screening compounds with cell-based assays and microscopy image-based analysis is an approach currently favored for drug discovery. Because of its high information yield, the strategy is called high-content screening (HCS).

Areas covered in this review: This review covers the application of HCS in drug discovery and also in basic research of potential new pathways that can be targeted for treatment of pathophysiological diseases. HCS faces several challenges, however, including the extraction of pertinent information from the massive amount of data generated from images. Several proposed approaches to HCS data acquisition and analysis are reviewed.

What the reader will gain: Different solutions from the fields of mathematics, bioinformatics and biotechnology are presented. Potential applications and limits of these recent technical developments are also discussed.

Take home message: HCS is a multidisciplinary and multistep approach for understanding the effects of compounds on biological processes at the cellular level. Reliable results depend on the quality of the overall process and require strong interdisciplinary collaborations.  相似文献   

18.
酶抑制剂类抗糖尿病药物是目前药物研究的热点,而药物筛选技术是制约此类抗糖尿病新药研发速度的关键步骤。主要从分子水平总结近年来报道的与糖尿病相关的酶抑制剂类候选药物的筛选方法,包括传统方法和前沿方法,着重介绍极具潜力的毛细管电泳法、质谱法、生物传感法和微通道筛选方法等。  相似文献   

19.
High-content screening moves to the front of the line   总被引:2,自引:0,他引:2  
Haney SA  LaPan P  Pan J  Zhang J 《Drug discovery today》2006,11(19-20):889-894
High-content screening (HCS) has been used in late-stage drug discovery for a decade. In the past few years, technological advances have expanded the role of HCS into the early stages of drug discovery, including high-throughput screening and hit-to-lead studies. More recently, computational advances in image analysis and technological advancements in general cell biology have extended the utility of HCS into target validation and basic biological studies, including RNAi screening. The use of HCS in target validation is expanding the work that can be done at this stage, especially the range of targets that can be characterized, and putting it into a more biological context.  相似文献   

20.
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