The "Specific" P-Glycoprotein Inhibitor Tariquidar Is Also a Substrate and an Inhibitor for Breast Cancer Resistance Protein (BCRP/ABCG2)
The "Specific" P-Glycoprotein Inhibitor Tariquidar Is Also a Substrate and an Inhibitor for Breast Cancer Resistance Protein (BCRP/ABCG2)
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DOI：
10.1021/cn100078a
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发表时间：
2011-02-01
影响因子：
5
通讯作者：
Hall, Matthew D.
中科院分区：
文献类型：
--
作者：
Kannan, Pavitra;Telu, Sanjay;Hall, Matthew D.
Tariquidar被开发为外排转运蛋白ABCB 1的特异性抑制剂。最近使用[C-11]-tariquidar测量小鼠ABCB 1（P-gp，P-glycoprotein）密度的正电子发射断层扫描脑成像研究表明，抑制剂可能不像以前认为的那样特异。我们研究了其作为人转运蛋白P-gp、乳腺癌耐药蛋白（BCRP，ABCG 2）和多药耐药蛋白1（MRP 1，ABCC 1）的抑制剂和底物的选择性。我们的研究结果表明，在低浓度下，tariquidar选择性地作为P-gp的抑制剂，也作为BCRP的底物。在更高的浓度（>= 100 nM）下，tariquidar可作为P-gp和BCRP的抑制剂。因此，tariquidar的体内特异性取决于浓度以及P-gp与BCRP的相对密度和容量。
Tariquidar was developed as a specific inhibitor of the efflux transporter ABCB1. Recent positron emission tomographic brain imaging studies using [C-11]-tariquidar to measure ABCB1 (P-gp, P-glycoprotein) density in mice indicate that the inhibitor may not be as specific as previously thought. We examined its selectivity as an inhibitor and a substrate for the human transporters P-gp, breast cancer resistance protein (BCRP, ABCG2), and multidrug resistance protein 1 (MRP1, ABCC1). Our results show that at low concentrations, tariquidar acts selectively as an inhibitor of P-gp and also as a substrate of BCRP. At much higher concentrations (>= 100 nM), tariquidar acts as an inhibitor of both P-gp and BCRP. Thus, the in vivo specificity of tariquidar depends on concentration and the relative density and capacity of P-gp vs BCRP.