Development of quantitative systems pharmacology and toxicology models within consortia: experiences and lessons learned through DILIsym development

Q3 Pharmacology, Toxicology and Pharmaceutics

Drug Discovery Today: Disease Models Pub Date : 2016-12-01 DOI:10.1016/j.ddmod.2017.04.001

Brett A. Howell , Scott Q. Siler , Hugh A. Barton , Elizabeth M. Joshi , Antonio Cabal , Gary Eichenbaum , Paul B. Watkins

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引用次数: 8

Abstract

The development of new pharmaceuticals for the treatment of human disease is increasingly challenging. New methods such as quantitative systems pharmacology (QSP) and quantitative systems toxicology (QST) can help address drug development challenges. Despite its promise, QSP/QST is not without its challenges. An investment is required to collect the necessary input data and ensure key components are represented qualitatively and quantitatively well. One strategy for addressing these concerns is conducting model development within consortia. Consortia offer companies the ability to share data, seek feedback from health authorities collectively, guide model development, learn from others, and share platform development costs. This article highlights lessons learned from past experiences associated with The DILI-sim Initiative – a collaborative effort focused on developing DILIsym software for predicting drug-induced liver injury (DILI).

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定量系统药理学和毒理学模型的发展:通过DILIsym发展的经验和教训

开发用于治疗人类疾病的新药越来越具有挑战性。定量系统药理学(QSP)和定量系统毒理学(QST)等新方法可以帮助解决药物开发挑战。尽管前景光明，QSP/QST也并非没有挑战。需要投资收集必要的输入数据，并确保关键组件在定性和定量上都得到很好的表示。解决这些问题的一个策略是在联盟中进行模型开发。联盟为公司提供了共享数据、集体向卫生当局寻求反馈、指导模型开发、向他人学习和分担平台开发成本的能力。本文重点介绍了与DILI-sim计划相关的过去经验教训。DILI-sim计划是一项合作努力，重点开发用于预测药物性肝损伤(DILI)的DILIsym软件。

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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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.