Recent advances in high throughput screening for ADME properties
Recent advances in high throughput screening for ADME properties
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DOI：
10.2174/138620708783877717
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发表时间：
2008-03-01
影响因子：
1.8
通讯作者：
Fisher, Michael B.
中科院分区：
文献类型：
--
作者：
Carlson, Timothy J.;Fisher, Michael B.
随着在典型的药物发现程序中合成的分子数量的增加，以及在药物候选物的选择中利用的大量信息，需要在发现中定期生成过多的药物代谢和药代动力学（DMPK）信息。在过去的十年中，许多体外，甚至在体内，DMPK屏幕已被开发和常规部署，以产生支持药物发现工作的信息。在过去的几年中，更新的方法，或适应的方法，已出版，这篇评论试图总结这些进展。特别是，已经报道了代谢清除、代谢抑制、体内暴露和分布的实验方法以及吸收、分布、代谢和排泄（ADME）性质的计算机测定的进展。生物分析方法，旨在优化分析物的方法开发，样品制备，和分析物检测，也有报道。未来的进展将进一步提高在药物发现早期对分子做出决定的能力。
With the increase in the numbers of molecules synthesized in a typical drug discovery program, as well as the large amount of information utilized in the selection of a drug candidate, there is a need for a plethora of drug metabolism and pharmacokinetic (DMPK) information to be regularly generated in discovery. Over the past decade, many in vitro, and even in vivo, DMPK screens have been developed and routinely deployed to generate this information in support of drug discovery efforts. In the past few years, newer methods, or adaptations to methods, have been published, and this review attempts to summarize these advances. In particular, advances have been reported for experimental approaches to metabolic clearance, CYP inhibition, in vivo exposure, and distribution, as well as in silico determinations of absorption, distribution, metabolism, and excretion (ADME) properties. Bioanalytical approaches aimed at optimizing analyte method development, sample preparation, and analyte detection, have also been reported. Future advances will further improve the ability to make decisions on molecules earlier in drug discovery.