Institute of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, Shandong Province, P.R. China.
Curr Med Chem. 2010;17(8):786-800. doi: 10.2174/092986710790514507.
P-glycoprotein (P-gp) is an ATP-driven transmembrane transporter capable of effluxing a wide variety of structurally diverse and functionally unrelated hydrophobic compounds out of the cell. Multidrug resistance (MDR), often associated with the over-expression of P-gp, has been implicated as a major obstacle to effective chemotherapy for cancer, parasitic diseases, AIDS, and other diseases. Drug efflux mediated by P-gp is also involved in decreasing the oral bioavailability of drugs by limiting intestinal absorption. Our appreciation of the structural and functional aspects of P-gp has definitely improved in recent years, benefiting from the deciphering of the structure of some bacterial transporters that paved the way for construction of homology models for more complex transporters. Here, we will review the recent advances in the studies of the structure and functional characteristics of P-gp with the hopes of facilitating rational drug design in developing novel potent MDR modulators.
P-糖蛋白（P-gp）是一种 ATP 驱动的跨膜转运蛋白，能够将多种结构不同和功能无关的疏水性化合物从细胞内排出。多药耐药（MDR）通常与 P-gp 的过度表达有关，它已被认为是癌症、寄生虫病、艾滋病和其他疾病有效化疗的主要障碍。P-gp 介导的药物外排也通过限制肠道吸收来降低药物的口服生物利用度。近年来，我们对 P-gp 的结构和功能方面的认识肯定有所提高，这得益于一些细菌转运蛋白结构的破译，为更复杂转运蛋白的同源模型的构建铺平了道路。在这里，我们将回顾 P-gp 结构和功能特性研究的最新进展，希望为开发新型有效的 MDR 调节剂的合理药物设计提供帮助。
