In silico prediction and control of ADME properties.
In silico prediction and control of ADME properties.
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ADME 特性的计算机预测和控制。
DOI：
10.2745/dds.18.22
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
M. Hashida
中科院分区：
文献类型：
--
作者：
F. Yamashita;M. Hashida
在过去的十年中，药物发现过程已被显着改变的新技术，如组合化学和高通量筛选。大量的化合物可以常规地合成和筛选。然而，这些技术发现的大多数候选药物具有不适当的药代动力学性质，因此在临床前和临床研究中失败。为了解决这个问题，必须在药物发现的早期阶段进行ADME筛查。虽然Caco-2细胞和重组P 450酶被用作高通量ADME筛选的体外模型，但虚拟组合文库的计算筛选在速度和成本方面越来越成为一种有吸引力的方法。本文综述了构效关系的分析方法以及溶解性、渗透性和代谢等药动学性质的模型。
During the last decade, drug discovery process has been dramatically changed by new technologies such as combinatorial chemistry and high throughput screening. A tremendous number of compounds can be synthesized and screened routinely. However, most of drug candidates found by these technologies possess inappropriate pharmacokinetic properties and therefore fail during pre-clinical and clinical studies. To solve this problem, ADME screening has to be performed in the earlier stage of drug discovery. While Caco-2 cells and recombinant P 450 enzymes are being used as in vitro models for high throughput ADME screening, computational screening of virtual combinatorial libraries is increasingly an attractive approach in terms of speed and cost. In this article, we review the methods of analyzing structure/property relationship and the models of pharmacokinetic properties such as solubility, permeability, and metabolism.