Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY 11439, USA.
Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY 11439, USA; School of Public Health, Guangzhou Medical University, Guangzhou, Guangdong 511436, China; Department of Cancer Biology, University of Toledo College of Medicine and Life Sciences, Toledo, OH 43614, USA.
Drug Resist Updat. 2021 Jan;54:100743. doi: 10.1016/j.drup.2021.100743. Epub 2021 Jan 13.
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 C, 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.
三磷酸腺苷结合盒（ABC）转运蛋白介导结构和机制不同的底物在逆浓度梯度的情况下通过 ATP 驱动的转运。在人类的七个 ABC 亚家族中，ABCC 是最大的亚家族，有 13 个成员。在这方面，由于其能够将各种化疗药物或其代谢物从肿瘤细胞中排出，因此 9 个 ABCC 成员被称为“多药耐药蛋白”（MRPs1-9）。此外，MRPs 还负责生理上重要的有机阴离子如白三烯 C、叶酸、胆汁酸和 cAMP 的 ATP 驱动外排。因此，MRPs 参与了重要的调节途径。阻断 MRPs 的抗癌药物外排功能在克服癌症多药耐药方面显示出了有希望的结果。因此，在过去的十年中，已经开发出了许多新型的 MRP 调节剂。在当前的综述中，我们总结了 MRPs 的结构、组织分布、生物学和药理学功能以及临床见解。此外，还讨论了最近关于 MRP 调节剂的更新及其在临床试验中的治疗应用。
