Cellular and Molecular Life Sciences CMLS

, Volume 58, Issue 7, pp 931–959

From MDR to MXR: new understanding of multidrug resistance systems, their properties and clinical significance

  • T. Litman
  • T. E. Druley
  • W. D. Stein
  • S. E. Bates

DOI: 10.1007/PL00000912

Cite this article as:
Litman, T., Druley, T., Stein, W. et al. CMLS, Cell. Mol. Life Sci. (2001) 58: 931. doi:10.1007/PL00000912


The ATP binding cassette (ABC) superfamily of membrane transporters is one of the largest protein classes known, and counts numerous proteins involved in the trafficking of biological molecules across cell membranes. The first known human ABC transporter was P-glycoprotein (P-gp), which confers multidrug resistance (MDR) to anticancer drugs. In recent years, we have obtained an increased understanding of the mechanism of action of P-gp as its ATPase activity, substrate specificity and pharmacokinetic interactions have been investigated. This review focuses on the functional characterization of P-gp, as well as other ABC transporters involved in MDR: the family of multidrug-resistance-associated proteins (MRP1-7), and the recently discovered ABC half-transporter MXR (also known as BCRP, ABCP and ABCG2). We describe recent progress in the analysis of protein structure-function relationships, and consider the conceptual problem of defining and identifying substrates and inhibitors of MDR. An in-depth discussion follows of how coupling of nucleotide hydrolysis to substrate transport takes place, and we propose a scheme for the mechanism of P-gp function. Finally, the clinical correlations, both for reversal of MDR in cancer and for drug delivery, are discussed.

Key words: Multidrug resistance; P-glycoprotein (MDR1); multidrug-resistance-associated protein (MRP); mitoxantrone resistance protein (MXR, BCRP, ABCP, ABCG2); ABC transporter; ATPase.

Copyright information

© Birkhäuser Verlag, 2001

Authors and Affiliations

  • T. Litman
    • 1
  • T. E. Druley
    • 2
  • W. D. Stein
    • 3
  • S. E. Bates
    • 4
  1. 1.Department of Medical Physiology, The Panum Institute 12.6.33, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen N (Denmark), Fax +45 3532 75 26, e-mail: t.litman@mfi.ku.dkDK
  2. 2.Dept. of Molecular Genetics, University of Illinois at Chicago, Chicago, (Illinois 60607, USA)US
  3. 3.Dept of Biological Chemistry, Institute of Life Sciences, Hebrew University, Jerusalem (Israel)IL
  4. 4.National Cancer Institute, Medicine Branch, NIH, Bethesda (Maryland 20892, USA)US