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动物模型在新型抗炎药物治疗慢性阻塞性肺疾病的药理学评价中的作用。

The role of animal models in the pharmacological evaluation of emerging anti-inflammatory agents for the treatment of COPD.

作者信息

Fox J Craig, Fitzgerald Mary F

机构信息

Argenta Discovery Ltd, Harlow, Essex, United Kingdom.

出版信息

Curr Opin Pharmacol. 2009 Jun;9(3):231-42. doi: 10.1016/j.coph.2009.03.001. Epub 2009 Apr 6.

Abstract

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease that has been relatively under researched compared to other inflammatory diseases. Indeed, thus far there have been no anti-inflammatory therapies specifically approved for COPD and the available anti-inflammatory therapies were originally developed for asthma. The challenges facing research in COPD are multi-faceted; the mechanisms underlying the complex and heterogeneous pathology of this disease require unravelling; the role of inflammation in disease progression needs to be confirmed and new drugs with potential to successfully treat COPD need to be identified. Many of the compounds in the clinic today have been identified through the work performed in a range of animal models of COPD. These models have provided us with an understanding of disease pathology and potential mechanistic pathways and have given us the means to prioritise new chemical entities before entry into the clinic. This review will summarise currently available models of COPD and highlight how they have been used to take a first generation of anti-inflammatory therapies for COPD into clinical development. The predictive nature of these animal models will become clear as these therapies are clinically evaluated. The recurring challenge will be to take emerging pre-clinical and clinical data and use it to continually improve animal models so that they remain a valuable tool in the drug discovery process.

摘要

慢性阻塞性肺疾病(COPD)是一种慢性炎症性疾病,与其他炎症性疾病相比,其研究相对较少。事实上,迄今为止,尚无专门批准用于COPD的抗炎疗法,现有的抗炎疗法最初是为哮喘开发的。COPD研究面临多方面挑战;该疾病复杂且异质性病理背后的机制需要阐明;炎症在疾病进展中的作用需要得到证实,且需要确定有潜力成功治疗COPD的新药。当今临床上的许多化合物都是通过在一系列COPD动物模型中开展的工作发现的。这些模型让我们了解了疾病病理和潜在的机制途径,并为我们提供了在进入临床前对新化学实体进行优先排序的方法。本综述将总结目前可用的COPD模型,并强调它们如何被用于将第一代COPD抗炎疗法推进到临床开发阶段。随着这些疗法进行临床评估,这些动物模型的预测性将变得清晰。反复出现的挑战将是利用新出现的临床前和临床数据,不断改进动物模型,使其在药物发现过程中始终是一个有价值的工具。

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