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传染病药理学的快速分析。

Rapid analysis of pharmacology for infectious diseases.

机构信息

Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, UK.

出版信息

Curr Top Med Chem. 2011;11(10):1292-300. doi: 10.2174/156802611795429130.

Abstract

Pandemic, epidemic and endemic infectious diseases are united by a common problem: how do we rapidly and cost-effectively identify potential pharmacological interventions to treat infections? Given the large number of emerging and neglected infectious diseases and the fact that they disproportionately afflict the poorest members of the global society, new ways of thinking are required to developed high productivity discovery systems that can be applied to a larger number of pathogens. The growing availability of parasite genome data provides the basis for developing methods to prioritize, a priori, the potential drug target and pharmacological landscape of an infectious disease. Thus the overall objective of infectious disease informatics is to enable the rapid generation of plausible, novel medical hypotheses of testable pharmacological experiments, by uncovering undiscovered relationships in the wealth of biomedical literature and databases that were collected for other purposes. In particular our goal is to identify potential drug targets present in a pathogen genome and prioritize which pharmacological experiments are most likely to discover drug-like lead compounds rapidly against a pathogen (i.e. which specific compounds and drug targets should be screened, in which assays and where they can be sourced). An integral part of the challenge is the development and integration of methods to predict druggability, essentiality, synthetic lethality and polypharmacology in pathogen genomes, while simultaneously integrating the inevitable issues of chemical tractability and the potential for acquired drug resistance from the start.

摘要

大流行、流行病和地方病传染病有一个共同的问题:我们如何快速、经济有效地确定潜在的药物干预措施来治疗感染?鉴于新出现的和被忽视的传染病数量众多,而且它们不成比例地影响着全球社会中最贫穷的成员,因此需要新的思维方式来开发能够应用于更多病原体的高生产力发现系统。寄生虫基因组数据的日益普及为开发方法提供了基础,这些方法可以预先确定传染病的潜在药物靶点和药物作用谱。因此,传染病信息学的总体目标是通过揭示为其他目的而收集的丰富生物医学文献和数据库中未被发现的关系,快速生成合理的、新颖的可测试药物实验的医学假说。特别是,我们的目标是确定病原体基因组中存在的潜在药物靶点,并确定哪些药物实验最有可能快速发现针对病原体的类药性先导化合物(即应筛选哪些特定化合物和药物靶点、在哪些检测中进行筛选以及可以从何处获得)。该挑战的一个组成部分是开发和整合预测病原体基因组中药物可开发性、必需性、合成致死性和多效性的方法,同时从一开始就整合化学可处理性和获得药物耐药性的必然问题。

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