Avoiding physicochemical artefacts in early ADME-Tox experiments

被引：22

作者：

DeWitte, Robert S. ^{[1
]}

机构：

[1] Thermo Electron Corp, New Pharma R&D Solut, Burlington, ON L7L 6A6, Canada

来源：

DRUG DISCOVERY TODAY | 2006年 / 11卷 / 17-18期

关键词：

D O I：

10.1016/j.drudis.2006.07.012

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Recent literature has highlighted the importance of fundamental physicochemical properties in HTS and ADME-Tox: high lipophilicity, low dimethyl sulfoxide solubility, low aqueous solubility, aggregation and nonspecific binding to proteins and phospholipids. Unless carefully controlled for, each of these artefacts can confound individual ADME-Tox results and their interpretation on aggregate. This article reviews the impact of these phenomena and suggests experimental strategies for minimizing the magnitude and frequency of these artefacts without compromising the essential speed of the experimental process. Many of the concepts translate directly to the HTS context.

引用

页码：855 / 859

页数：5

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