Certara UK Limited, Simcyp Division, 1 Concourse Way, Sheffield, S1 2BJ, UK.
Certara UK Limited, Simcyp Division, 1 Concourse Way, Sheffield, S1 2BJ, UK; Centre for Applied Pharmacokinetic Research (CAPKR), School of Health Sciences, University of Manchester, Stopford Building, Oxford Road, Manchester, M13 9PT, UK.
Drug Discov Today Technol. 2021 Dec;39:13-22. doi: 10.1016/j.ddtec.2021.06.002. Epub 2021 Jun 25.
Translation of information on drug exposure and effect is facilitated by in silico models that enable extrapolation of in vitro measurements to in vivo clinical outcomes. These models integrate drug-specific data with information describing physiological processes and pathological changes, including alterations to proteins involved in drug absorption, distribution and elimination. Over the past 15 years, quantitative proteomics has contributed a wealth of protein expression data, which are currently used for a variety of systems pharmacology applications, as a complement or a surrogate for activity of the corresponding proteins. In this review, we explore current and emerging applications of targeted and global (untargeted) proteomics in translational pharmacology as well as strategies for improved integration into model-based drug development.
通过能够将体外测量值外推到体内临床结果的计算机模型，可以促进药物暴露和效果信息的翻译。这些模型将药物特异性数据与描述生理过程和病理变化的信息（包括涉及药物吸收、分布和消除的蛋白质的改变）相结合。在过去的 15 年中，定量蛋白质组学提供了大量的蛋白质表达数据，这些数据目前被用于各种系统药理学应用，作为相应蛋白质活性的补充或替代。在这篇综述中，我们探讨了靶向和全局（非靶向）蛋白质组学在转化药理学中的当前和新兴应用，以及将其更好地整合到基于模型的药物开发中的策略。
