The potential impact of drug transporters on nucleoside-analog-based antiviral chemotherapy

被引：44
作者：
Borst, P
Balzarini, J
Ono, N
Reid, G
de Vries, H
Wielinga, P
Wijnholds, J
Zelcer, N
机构：
[1] Netherlands Canc Inst, Div Mol Biol, NL-1066 CX Amsterdam, Netherlands
[2] Katholieke Univ Leuven, Rega Inst, B-3000 Louvain, Belgium
[3] Christchurch Sch Med, Dept Paediat, Childrens Canc Res Grp, Christchurch, New Zealand
[4] Netherlands Ophthalm Res Inst, Dept Ophthalmogenet, NL-1105 BA Amsterdam, Netherlands
来源：
ANTIVIRAL RESEARCH | 2004年 / 62卷 / 01期
关键词：
ABC transporters; cyclic nucleotides; MRPs; nucleoside analogs; oral drug availability;
D O I：
10.1016/j.antiviral.2003.11.002
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
Several ATP-binding cassette (ABC) transporters can transport drugs out of cells against steep concentration gradients resulting in resistance to the drugs transported. Recent work has shown that at least three members of the family of human Multidrug Resistance- associated Proteins (MRPs), MRP4, 5 and 8, are able to transport some nucleoside-monophosphate analogs. This can result in resistance to the base, nucleoside or nucleotide precursors of these results, at least in cell lines with high levels of transporter. The affinity of these transporters for the nucleotide analogs studied thus far is relatively low (millimolar rather than micromolar), and this limits their potential impact on the resistance. We briefly review how ABC transporters in general, and MRPs in particular, could affect the disposition and cellular accumulation of antiviral compounds. (C) 2003 Elsevier B.V. All rights reserved.
引用
收藏
页码：1 / 7
页数：7
相关论文
共 52 条
[31]   Role of glutathione in the multidrug resistance protein 4 (MRP4/ABCC4)mediated efflux of cAMP and resistance to purine analogues [J].
Lai, LQ ;
Tan, TM .
BIOCHEMICAL JOURNAL, 2002, 361 (03) :497-503
[32]  
Lorico A, 1997, CANCER RES, V57, P5238
[33]  
Lorico A, 1996, CANCER RES, V56, P5351
[34]   Multidrug resistance protein MRP2 contributes to blood-brain barrier function and restricts antiepileptic drug activity [J].
Potschka, H ;
Fedrowitz, M ;
Löscher, W .
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2003, 306 (01) :124-131
[35]   Characterization of the transport of nucleoside analog drugs by the human multidrug resistance proteins MRP4 and MRP5 [J].
Reid, G ;
Wielinga, P ;
Zelcer, N ;
De Haas, M ;
Van Deemter, L ;
Wijnholds, J ;
Balzarini, J ;
Borst, P .
MOLECULAR PHARMACOLOGY, 2003, 63 (05) :1094-1103
[36]   The human multidrug resistance protein MRP4 functions as a prostaglandin efflux transporter and is inhibited by nonsteroidal antiinflammatory drugs [J].
Reid, G ;
Wielinga, P ;
Zelcer, N ;
van der Heijden, I ;
Kuil, A ;
de Haas, M ;
Wijnholds, J ;
Borst, P .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (16) :9244-9249
[37]   Mammalian drug efflux transporters of the ATP binding cassette (ABC) family: an overview [J].
Schinkel, AH ;
Jonker, JW .
ADVANCED DRUG DELIVERY REVIEWS, 2003, 55 (01) :3-29
[38]   MRP4: A previously unidentified factor in resistance to nucleoside-based antiviral drugs [J].
Schuetz, JD ;
Connelly, MC ;
Sun, DX ;
Paibir, SG ;
Flynn, PM ;
Srinivas, RV ;
Kumar, A ;
Fridland, A .
NATURE MEDICINE, 1999, 5 (09) :1048-1051
[39]   Characterization of the mouse Abcc12 gene and its transcript encoding an ATP-binding cassette transporter, an orthologue of human ABCC12 [J].
Shimizu, H ;
Taniguchi, H ;
Hippo, Y ;
Hayashizaki, Y ;
Aburatani, H ;
Ishikawa, T .
GENE, 2003, 310 :17-28
[40]   ABCG2 transports sulfated conjugates of steroids and xenobiotics [J].
Suzuki, M ;
Suzuki, H ;
Sugimoto, Y ;
Sugiyama, Y .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (25) :22644-22649
123456