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Inhibit or Evade Multidrug Resistance P-Glycoprotein in Cancer Treatment.

Abstract：

:Multidrug resistance (MDR) is a major cause of failure in cancer chemotherapy. P-glycoprotein (P-gp), a promiscuous drug efflux pump, has been extensively studied for its association with MDR due to overexpression in cancer cells. Several P-gp inhibitors or modulators have been investigated in clinical trials in hope of circumventing MDR, with only limited success. Alternative strategies are actively pursued, such as the modification of existing drugs, development of new drugs, or combination of novel drug delivery agents to evade P-gp-dependent efflux. Despite the importance and numerous studies, these efforts have mostly been undertaken without a priori knowledge of how drugs interact with P-gp at the molecular level. This review highlights and discusses progress toward and challenges impeding drug development for inhibiting or evading P-gp in the context of our improved understanding of the structural basis and mechanism of P-gp-mediated MDR.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Waghray D,Zhang Q

doi

10.1021/acs.jmedchem.7b01457

subject

Has Abstract

pub_date

2018-06-28 00:00:00

pages

5108-5121

issue

12

eissn

0022-2623

issn

1520-4804

journal_volume

61

pub_type

杂志文章,评审

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