Modulators of P-glycoprotein-associated multidrug resistance.
Modulators of P-glycoprotein-associated multidrug resistance.
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DOI：
10.1007/978-1-4615-3872-1_7
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发表时间：
1991
影响因子：
--
通讯作者：
W. T. Beck
中科院分区：
文献类型：
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作者：
W. T. Beck
与P-糖蛋白过度表达相关的多药耐药（Pgp-MDR）是一个有充分证据的实验现象，其药理学、生物化学和分子基础是已知的。它的重要性在于它似乎具有临床相关性，因此逆转或规避Pgp-MDR的尝试显然具有高度优先性。有大量的实验工作表明，某些类型的膜活性药物能够在不同程度上规避MDR，但这些药物是否在临床上有用还有待观察。本章的目的是讨论这些调节剂的作用。Pgp-MDR的一般特征将被简要概述，并强调其与最近描述的其他形式的MDR的区别。主要的重点将是可以调节Pgp-MDR的化合物。我们目前的理解机制（S），这些代理商在MDR细胞的工作将进行总结，目前的调制器设计模型将进行讨论，并与这些代理商正在进行的一些临床研究，以及随之而来的问题将被概述。最后对今后调制剂的研究方向提出了一些思考。
Multidrug resistance associated with overexpression of P-glycoprotein (Pgp-MDR) is a well-documented experimental phenomenon whose pharmacologic, biochemical, and molecular basis is known. Its importance resides in the fact that it appears to have clinical correlates, so attempts to reverse or circumvent Pgp-MDR clearly assume high priority. There is a considerable body of experimental work showing that certain classes of membrane-active drugs are capable of circumventing MDR to varying degrees, but it remains to be seen whether these agents will be useful clinically. The goal in this chapter is to discuss the actions of these modulators. The general features of Pgp-MDR will be briefly outlined and its and differences from other forms of MDR recently described will be highlighted. The main focus will be on compounds that can modulate Pgp-MDR. Our current understanding of the mechanism(s) by which these agents work in MDR cells will be summarized, current models for modulator design will be discussed, and some of the ongoing clinical studies with these agents, as well as their attendant problems will be outlined. The conclusion offers some thoughts about future directions of modulator studies.