Out‐compute drug side effects: Focus on cytochrome P450 2D6 modeling,Wiley Interdisciplinary Reviews: Computational Molecular Science

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Out‐compute drug side effects: Focus on cytochrome P450 2D6 modeling
Wiley Interdisciplinary Reviews: Computational Molecular Science ( IF 16.8 ) Pub Date : 2018-05-03 , DOI: 10.1002/wcms.1366
Charleen G. Don ₁ , Martin Smieško ₁

Affiliation

Understanding the way in which drugs are metabolized by cytochrome P450 2D6 (CYP2D6) and hence the underlying mechanisms that define potential toxicity is crucial to avoid adverse reactions. The high occurrence of CYP2D6 polymorphs enhances the complexity of the toxicity assessment of a drug candidate and should be tackled from early drug discovery phase on. The recent increase in available mammalian CYP2D6 X‐ray structures opens the gateway to the development of in silico three‐dimensional CYP2D6 toxicity prediction techniques that address also the major clinically relevant allelic variants. This review presents the basic principles needed for comprehending the enzyme particularities, gives a concise overview of several clinical relevant allelic CYP2D6 variants, and explores the state‐of‐the‐art CYP2D6 research field to accelerate the development and use of such integrative in silico modeling technologies.

中文翻译：

药物外计算副作用：专注于细胞色素P450 2D6建模

了解药物通过细胞色素P450 2D6（CYP2D6）代谢的方式以及因此定义潜在毒性的潜在机制对于避免不良反应至关重要。CYP2D6多态性的高发生率增加了候选药物毒性评估的复杂性，应从早期药物发现阶段就予以解决。可用的哺乳动物CYP2D6 X射线结构的最新增加为计算机化的发展打开了大门三维CYP2D6毒性预测技术，可解决主要的临床相关等位基因变体。这篇综述提出了理解酶特异性的基本原理，简要概述了几种临床相关的等位基因CYP2D6变体，并探索了最新的CYP2D6研究领域，以加速这种一体化计算机模拟的开发和使用。技术。

更新日期：2018-05-03

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