基于膜转运体在药物吸收、分布、代谢和排泄过程中功能的药物设计

doi:10.5246/jcps.2012.06.069

摘要/Abstract

摘要：

膜转运体介导了多种药物的摄取和外排过程, 在药物吸收、分布、代谢和排泄 (ADME) 过程中起了重要作用。膜转运体的独特性质使其成为药物研发中的潜在靶标, 合理利用这一靶标可使药物具有理想的药动学特征包括靶向分布, 临床疗效改进和不良反应的降低。本文综述了目前主要的摄取和外排转运体包括溶质转运蛋白 (SLC) 超家族和三磷酸腺苷结合盒超家族 (ABC) 的特异性组织分布, 转运功能和底物谱。例举了几个基于转运体的改良药物ADME特性的成功例子。在本文最后探讨了药物设计研发中常用于研究药物和转运体之间相互作用的体内体外的研究方法。

关键词: ABC转运体, SLC转运体, 摄取, 外排, 药物设计

Abstract:

Membrane transporters mediate the influx and efflux of various drugs, and play essential roles in drug absorption, distribution, metabolism and excretion (ADME). The unique characteristics of membranes transporters potentiate them as targets for developing drugs with ideal pharmacokinetics profiles, including targeted distribution, improved clinical efficacy and low adverse reaction. In this review, we summarize the tissue-specific expression, transport functions and substrates profiles of the major influx and efflux transporters, including solute carrier (SLC) superfamily and adenosine triphosphate (ATP)-binding cassette (ABC) superfamily. Moreover, we describe examples of successful drug or prodrug design based on the function of transporters that yielded drugs with excellent ADME properties. Lastly, we discuss the in vitro and in vivo methods that are broadly applied in the drug designing process to study the interactions between the drugs and the transporters.

Key words: ABC transporter, SLC transporter, Influx, Efflux, Drug design

中图分类号:

R916.1

Supporting:

Foundation item: National Science and Technology Major Project (Grant No. 2012ZX09506001-004).

^*Corresponding author. Tel.: 86-571-88208407; Fax: 86-571-88208408

孙冬黎, 蒋惠娣^*, 曾苏^*

. 基于膜转运体在药物吸收、分布、代谢和排泄过程中功能的药物设计[J]. , DOI: 10.5246/jcps.2012.06.069.

Dongli Sun, Huidi Jiang^*, Su Zeng^*. Drug design based on the function of membrane transporters in drug absorption, distribution, metabolism and excretion [J]. , DOI: 10.5246/jcps.2012.06.069.

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