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Anticancer multidrug resistance mediated by MRP1: Recent advances in the discovery of reversal agents
Multidrug resistance protein 1 (MRP1) belongs to the ATP‐binding cassette (ABC) transporter family. It is able to transport a broad range of anticancer drugs through cellular membranes, thus limiting their antiproliferative action. Since its discovery in 1992, MRP1 has been the most studied among MR...
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Published in: | Medicinal research reviews 2005-07, Vol.25 (4), p.453-472 |
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creator | Boumendjel, Ahcène Baubichon-Cortay, Hélène Trompier, Doriane Perrotton, Thomas Di Pietro, Attilio |
description | Multidrug resistance protein 1 (MRP1) belongs to the ATP‐binding cassette (ABC) transporter family. It is able to transport a broad range of anticancer drugs through cellular membranes, thus limiting their antiproliferative action. Since its discovery in 1992, MRP1 has been the most studied among MRP proteins, which now count nine members. Besides the biological work, which targets structure elucidation, binding sites location, and mode of action, most efforts have been focused on finding molecules which act as MRP1 inhibitors. In this review, we attempt to summarize and highlight studies dealing with modulators of MRP1‐mediated multidrug resistance (MDR), which have been accomplished in the last 5 years. The reported MRP1 inhibitors are discussed according to their chemical class. Finally, we try to bring information on structure–activity relationship (SAR) aspects and how modulators might interact with MRP1. This study may facilitate the rational design of future modulators of MDR. © 2005 Wiley Periodicals, Inc. |
doi_str_mv | 10.1002/med.20032 |
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Res. Rev</addtitle><description>Multidrug resistance protein 1 (MRP1) belongs to the ATP‐binding cassette (ABC) transporter family. It is able to transport a broad range of anticancer drugs through cellular membranes, thus limiting their antiproliferative action. Since its discovery in 1992, MRP1 has been the most studied among MRP proteins, which now count nine members. Besides the biological work, which targets structure elucidation, binding sites location, and mode of action, most efforts have been focused on finding molecules which act as MRP1 inhibitors. In this review, we attempt to summarize and highlight studies dealing with modulators of MRP1‐mediated multidrug resistance (MDR), which have been accomplished in the last 5 years. The reported MRP1 inhibitors are discussed according to their chemical class. Finally, we try to bring information on structure–activity relationship (SAR) aspects and how modulators might interact with MRP1. 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subjects | Animals ATP-Binding Cassette, Sub-Family B, Member 1 - antagonists & inhibitors Drug Design Drug Resistance, Multiple - drug effects Drug Resistance, Neoplasm - drug effects Flavonoids - pharmacology Humans MRP1 multidrug resistance modulators Raloxifene Hydrochloride - pharmacology Structure-Activity Relationship structure-activity relationship (SAR) Verapamil - pharmacology |
title | Anticancer multidrug resistance mediated by MRP1: Recent advances in the discovery of reversal agents |
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