Inhibitors of Multidrug Efflux Transporters: Their Membrane and Protein Interactions

Authors: A. Seelig1; E. Gatlik-Landwojtowicz1

Source: Mini Reviews in Medicinal Chemistry, Volume 5, Number 2, February 2005 , pp. 135-151(17)

Publisher: Bentham Science Publishers

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Abstract:

Modulators and inhibitors of multidrug efflux transporters, like P-glycoprotein, are used to reduce or inhibit multidrug resistance, MDR, which leads to a failure of the chemotherapy of e.g. cancers, epilepsy, bacterial, parasitic, and fungal diseases. Binding and transport of first-, second-, and third-generation modulators and inhibitors of P-glycoprotein are discussed, taking into account the properties of the drug (Hbonding potential, dimensions, and pKagr values) as well as the properties of the membrane.

Keywords: p-glycoprotein; first; second; and third-generation inhibitors; modulators; membrane partitioning; transporter binding; transport kinetics

Document Type: Review article

DOI: 10.2174/1389557053402693

Affiliations: 1: Biophysical Chemistry, Biozentrum, University of Basel, Klingelbergstrasse 50-70, CH-4056 Basel, Switzerland.

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