向着知识驱动的跨物种外推

Q3 Pharmacology, Toxicology and Pharmaceutics Drug Discovery Today: Disease Models Pub Date : 2016-12-01 DOI:10.1016/j.ddmod.2017.02.008

Christoph Thiel , Ute Hofmann , Ahmed Ghallab , Rolf Gebhardt , Jan G. Hengstler , Lars Kuepfer

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引用次数: 6

摘要

从临床前研究到临床阶段的过渡是药物开发的关键步骤。在第一阶段，经过一年的体外和临床前动物模型开发，一种新的分子实体将首次用于人类。然而，在此类首次人体试验期间，大量项目被关闭，主要是由于毒性原因。这就需要在药物开发中采用新的方法，分别通过计算建模和选择解释性动物模型，以支持从临床前阶段过渡到临床阶段。在这篇综述中，我们将讨论跨物种外推的基本挑战，然后介绍该领域的一些最新进展以及未来的展望。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Towards knowledge-driven cross-species extrapolation

The transition from preclinical research to clinical phases is a crucial step in pharmaceutical development. In phase I, a new molecular entity is for the first administered to humans, after year-long development in in vitro and in preclinical animal models. However, a significant number of projects is closed during such first-in-man trials, mostly due to reasons of toxicity. This requires for new approaches in pharmaceutical development through computational modelling and through the selection of explanatory animal models, respectively, in order to support the transition from preclinical to clinical phases. In this review we will discuss the basic challenges in cross-species extrapolation before presenting some recent developments in this field as well as future perspectives.

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来源期刊

Drug Discovery Today: Disease Models Pharmacology, Toxicology and Pharmaceutics-Drug Discovery

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期刊介绍： Drug Discovery Today: Disease Models discusses the non-human experimental models through which inference is drawn regarding the molecular aetiology and pathogenesis of human disease. It provides critical analysis and evaluation of which models can genuinely inform the research community about the direct process of human disease, those which may have value in basic toxicology, and those which are simply designed for effective expression and raw characterisation.