Determination and modelling of stereoselective interactions of ligands with drug transporters: A key dimension in the understanding of drug disposition

被引：9

作者：

Bhatia, P. ^{[1
]}

Kolinski, M. ^{[2
]}

Moaddel, R. ^{[1
]}

Jozwiak, K. ^{[3
]}

Wainer, I. W. ^{[1
]}

机构：

[1] NIA, Natl Inst Hlth, Gerontol Res Ctr, Baltimore, MD 21224 USA

[2] Int Inst Mol & Cell Biol, Warsaw, Poland

[3] Med Univ Lublin, Lublin, Poland

来源：

XENOBIOTICA | 2008年 / 38卷 / 7-8期

关键词：

P-glycoprotein; organic cation transporter; cellular membrane affinity chromatography; quantitative structure-activity relationship (QSAR); pharmacophore modelling; enantioselectivity; chirality;

D O I：

10.1080/00498250802109207

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

1. Stereochemistry is an important dimension in pharmacology and plays a role in every aspect of the pharmacological fate of chiral xenobiotics. This includes small molecule-drug transporter binding. 2. This paper reviews the reported stereoselectivities of substrate and inhibitor interactions with P-glycoprotein and the organic cation transporter obtained using standard functional and binding studies, as well as data obtained from online cellular membrane affinity chromatography studies. 3. The use of stereochemical data in quantitative structure-activity relationship (QSAR) and pharmacophore modelling is also addressed as is the effect of ignoring the fact that small molecule-drug transporter interactions take place in three-dimensional and asymmetric space.

引用

页码：656 / 675

页数：20

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