Boumendjel Ahcène, Baubichon-Cortay Hélène, Trompier Doriane, Perrotton Thomas, Di Pietro Attilio
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
Med Res Rev. 2005 Jul;25(4):453-72. doi: 10.1002/med.20032.
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.
多药耐药蛋白1（MRP1）属于ATP结合盒（ABC）转运蛋白家族。它能够将多种抗癌药物转运穿过细胞膜，从而限制其抗增殖作用。自1992年被发现以来，MRP1一直是MRP蛋白家族中研究最多的成员，目前该家族有九个成员。除了针对结构解析、结合位点定位和作用模式的生物学研究工作外，大部分努力都集中在寻找作为MRP1抑制剂的分子上。在这篇综述中，我们试图总结和突出过去5年中关于MRP1介导的多药耐药（MDR）调节剂的研究。根据化学类别对报道的MRP1抑制剂进行了讨论。最后，我们试图提供关于构效关系（SAR）方面的信息以及调节剂可能与MRP1相互作用的方式。这项研究可能有助于未来MDR调节剂的合理设计。
