P-glycoprotein(P-gp or ABCB1)is a member of the broad family of ABC transporters.P-gp participates in the establishment of physiological barriers limiting cellular access of a large number of toxic compounds.It thus p...P-glycoprotein(P-gp or ABCB1)is a member of the broad family of ABC transporters.P-gp participates in the establishment of physiological barriers limiting cellular access of a large number of toxic compounds.It thus plays important roles in the pharmacokinetics of these compounds.Cancer cells and cells infected by viruses exploit the presence of P-gp to fend off drug treatment,rendering them multidrug-resistant.Overcoming multidrug resistance caused by expression of ABC transporters has gained increasing attention in the field of drug development.Recently,studies of P-gp,especially from structural investigations by both cryo-electron microscopy and X-ray crystallography,have provided high-resolution mechanistic details for the function of this transporter.Structures with increasing resolution and accuracy in various substrate-and inhibitor-bound forms are available for analysis and a consensus on the mechanism of substrate polyspecificity is emerging.The use of new structural information may aid development of P-gp inhibitors as well as compounds that may bypass P-gp action.展开更多
基金This work was supported by the Intramural Research Program of the National Institutes of Health,National Cancer Institute,Center for Cancer Research.
文摘P-glycoprotein(P-gp or ABCB1)is a member of the broad family of ABC transporters.P-gp participates in the establishment of physiological barriers limiting cellular access of a large number of toxic compounds.It thus plays important roles in the pharmacokinetics of these compounds.Cancer cells and cells infected by viruses exploit the presence of P-gp to fend off drug treatment,rendering them multidrug-resistant.Overcoming multidrug resistance caused by expression of ABC transporters has gained increasing attention in the field of drug development.Recently,studies of P-gp,especially from structural investigations by both cryo-electron microscopy and X-ray crystallography,have provided high-resolution mechanistic details for the function of this transporter.Structures with increasing resolution and accuracy in various substrate-and inhibitor-bound forms are available for analysis and a consensus on the mechanism of substrate polyspecificity is emerging.The use of new structural information may aid development of P-gp inhibitors as well as compounds that may bypass P-gp action.
