The "Specific" P-Glycoprotein Inhibitor Tariquidar Is Also a Substrate and an Inhibitor for Breast Cancer Resistance Protein (BCRP/ABCG2)

被引：144

作者：

Kannan, Pavitra ^{[1
,2
]}

Telu, Sanjay ^{[1
]}

Shukla, Suneet ^{[3
]}

Ambudkar, Suresh V. ^{[3
]}

Pike, Victor W. ^{[1
]}

Halldin, Christer ^{[2
]}

Gottesman, Michael M. ^{[3
]}

Innis, Robert B. ^{[1
]}

Hall, Matthew D. ^{[3
]}

机构：

[1] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA

[2] Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden

[3] NCI, Cell Biol Lab, Bethesda, MD 20892 USA

来源：

ACS CHEMICAL NEUROSCIENCE | 2011年 / 2卷 / 02期

基金：

美国国家卫生研究院;

关键词：

Positron emission tomography; drug transporters; P-glycoprotein; breast cancer resistance protein; blood-brain barrier; transport inhibitors; tariquidar; BLOOD-BRAIN-BARRIER; DRUG EFFLUX TRANSPORTERS; MULTIDRUG-RESISTANCE; XR9576; ABCG2; RADIOTRACERS; LYMPHOCYTES; REVERSAL;

D O I：

10.1021/cn100078a

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：82 / 89

页数：8

共 33 条

[21] Drug resistance in brain diseases and the role of drug efflux transporters [J].