Targeting multidrug resistance protein 1 (MRP1, ABCC1): past, present, and future

Annu Rev Pharmacol Toxicol. 2014:54:95-117. doi: 10.1146/annurev-pharmtox-011613-135959. Epub 2013 Sep 18.

Abstract

The human ATP-binding cassette transporter multidrug resistance protein 1 (MRP1), encoded by ABCC1, was initially identified because of its ability to confer multidrug resistance in lung cancer cells. It is now established that MRP1 plays a role in protecting certain tissues from xenobiotic insults and that it mediates the cellular efflux of the proinflammatory cysteinyl leukotriene C4 as well as a vast array of other endo- and xenobiotic organic anions. Many of these are glutathione (GSH) or glucuronide conjugates, the products of Phase II drug metabolism. MRP1 also plays a role in the cellular efflux of the reduced and oxidized forms of GSH and thus contributes to the many physiological and pathophysiological processes influenced by these small peptides, including oxidative stress. In this review, the pharmacological and physiological aspects of MRP1 are considered in the context of the current status and future prospects of pharmacological and genetic modulation of MRP1 activity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Clinical Trials as Topic
  • Disease Models, Animal
  • Drug Resistance, Neoplasm
  • Glutathione / metabolism
  • Humans
  • Leukotriene C4 / metabolism
  • Molecular Targeted Therapy*
  • Multidrug Resistance-Associated Proteins / antagonists & inhibitors
  • Multidrug Resistance-Associated Proteins / genetics
  • Multidrug Resistance-Associated Proteins / metabolism*
  • Substrate Specificity

Substances

  • Multidrug Resistance-Associated Proteins
  • Leukotriene C4
  • Glutathione
  • multidrug resistance-associated protein 1