title: Anticancer multidrug resistance mediated by MRP1: recent advances in the discovery of reversal agents.
abstract: 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.
authors.affiliation: Département de Pharmacochimie Moléculaire, UMR 5063 CNRS/Université Joseph Fourier-Grenoble I, 5 Avenue de Verdun BP 138, 38243 Meylan, France. Ahcène.Boumendjelujf-grenoble.fr
authors.forename: Ahcène
authors.initials: A
authors.lastname: Boumendjel
authors.forename: Hélène
authors.initials: H
authors.lastname: Baubichon-Cortay
authors.forename: Doriane
authors.initials: D
authors.lastname: Trompier
authors.forename: Thomas
authors.initials: T
authors.lastname: Perrotton
authors.forename: Attilio
authors.initials: A
authors.lastname: Di Pietro
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors*; D000818:Animals; D015195:Drug Design; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D020849:Raloxifene Hydrochloride / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014700:Verapamil / Q000494:pharmacology
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D005419:Flavonoids; D020849:Raloxifene Hydrochloride; D014700:Verapamil