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Anticancer multidrug resistance mediated by MRP1: Recent advances in the discovery of reversal agents
Author(s) -
Boumendjel Ahcène,
BaubichonCortay Hélène,
Trompier Doriane,
Perrotton Thomas,
Di Pietro Attilio
Publication year - 2005
Publication title -
medicinal research reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.868
H-Index - 130
eISSN - 1098-1128
pISSN - 0198-6325
DOI - 10.1002/med.20032
Subject(s) - multiple drug resistance , limiting , mode of action , atp binding cassette transporter , rational design , transporter , small molecule , computational biology , biology , pharmacology , site of action , drug resistance , biochemistry , genetics , gene , mechanical engineering , engineering , endocrinology
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.