Borst P, Balzarini J, Ono N, Reid G, de Vries H, Wielinga P, Wijnholds J, Zelcer N
Division of Molecular Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
Antiviral Res. 2004 Apr;62(1):1-7. doi: 10.1016/j.antiviral.2003.11.002.
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.
几种ATP结合盒（ABC）转运蛋白可将药物逆着陡峭的浓度梯度转运出细胞，从而导致对所转运药物产生耐药性。最近的研究表明，人类多药耐药相关蛋白（MRP）家族中的至少三个成员，即MRP4、5和8，能够转运一些单磷酸核苷类似物。这可能导致对这些物质的碱基、核苷或核苷酸前体产生耐药性，至少在具有高水平转运蛋白的细胞系中如此。迄今为止，这些转运蛋白对所研究的核苷酸类似物的亲和力相对较低（毫摩尔而非微摩尔），这限制了它们对耐药性的潜在影响。我们简要回顾一下ABC转运蛋白，特别是MRP，如何影响抗病毒化合物的处置和细胞内蓄积。
