ATP-binding cassette (ABC) transporters mediate the ATP-driven translocation of structurally and mechanistically distinct substrates against steep concentration gradients. Among the seven human ABC subfamilies namely ABCA-ABCG, ABCC is the largest subfamily with 13 members. In this respect, 9 of the ABCC members are termed “multidrug resistance proteins” (MRPs1-9) due to their ability to mediate cancer multidrug resistance (MDR) by extruding various chemotherapeutic agents or their metabolites from tumor cells. Furthermore, MRPs are also responsible for the ATP-driven efflux of physiologically important organic anions such as leukotriene C₄, folic acid, bile acids and cAMP. Thus, MRPs are involved in important regulatory pathways. Blocking the anticancer drug efflux function of MRPs has shown promising results in overcoming cancer MDR. As a result, many novel MRP modulators have been developed in the past decade. In the current review, we summarize the structure, tissue distribution, biological and pharmacological functions as well as clinical insights of MRPs. Furthermore, recent updates in MRP modulators and their therapeutic applications in clinical trials are also discussed.

ATP 结合盒 (ABC) 转运蛋白介导 ATP 驱动的结构和机械上不同底物的易位，以抵抗陡峭的浓度梯度。在七个人类 ABC 亚科 ABCA-ABCG 中，ABCC 是最大的亚科，有 13 个成员。在这方面，ABCC 成员中有 9 个被称为“多药耐药蛋白”（MRPs1-9），因为它们能够通过从肿瘤细胞中挤出各种化疗药物或其代谢物来介导癌症多药耐药（MDR）。此外，MRP 还负责 ATP 驱动的生理学上重要的有机阴离子如白三烯 C _{4 的}流出、叶酸、胆汁酸和 cAMP。因此，MRP 参与重要的调控途径。阻断 MRP 的抗癌药物外排功能在克服癌症 MDR 方面显示出有希望的结果。因此，在过去十年中开发了许多新型 MRP 调制器。在当前的综述中，我们总结了 MRP 的结构、组织分布、生物学和药理学功能以及临床见解。此外，还讨论了 MRP 调节剂的最新更新及其在临床试验中的治疗应用。