Sex-Dependent Expression and Activity of the ATP-Binding Cassette Transporter Breast Cancer Resistance Protein (BCRP/ABCG2) in Liver

2005 ◽  
Vol 67 (5) ◽  
pp. 1765-1771 ◽  
Author(s):  
Gracia Merino ◽  
Antonius E. van Herwaarden ◽  
Els Wagenaar ◽  
Johan W. Jonker ◽  
Alfred H. Schinkel
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Resistance Protein ◽  
Atp Binding ◽  
Cancer Resistance ◽  
Atp Binding Cassette Transporter ◽  
Resistance Protein ◽  
Expression And Activity ◽  
Atp Binding Cassette

Interaction of Thiazolidinediones (Glitazones) with the ATP-Binding Cassette Transporters P-Glycoprotein and Breast Cancer Resistance Protein

Pharmacology ◽  
2009 ◽  
Vol 84 (5) ◽  
pp. 264-270 ◽  
Author(s):  
Johanna Weiss ◽  
Alexandra Sauer ◽  
Melanie Herzog ◽  
Rainer H. Böger ◽  
Walter E. Haefeli ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Resistance Protein ◽  
Atp Binding ◽  
Cancer Resistance ◽  
P Glycoprotein ◽  
Atp Binding Cassette Transporters ◽  
Resistance Protein ◽  
Atp Binding Cassette

scholarly journals Expression and Activity of Breast Cancer Resistance Protein (BCRP/ABCG2) in Human Distal Lung Epithelial Cells In Vitro

2017 ◽  
Vol 34 (12) ◽  
pp. 2477-2487 ◽  
Author(s):  
Sabrina Nickel ◽  
Mohammed Ali Selo ◽  
Juliane Fallack ◽  
Caoimhe G. Clerkin ◽  
Hanno Huwer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epithelial Cells ◽  
Breast Cancer Resistance Protein ◽  
Lung Epithelial Cells ◽  
Cancer Resistance ◽  
Lung Epithelial ◽  
Resistance Protein ◽  
Distal Lung ◽  
Expression And Activity

scholarly journals Tyrosine and aurora kinase inhibitors diminish transport function of multidrug resistance-associated protein (MRP) 4 and breast cancer resistance protein (BCRP)

ADMET & DMPK ◽  
2016 ◽  
Vol 4 (4) ◽  
pp. 302
Author(s):  
Rhiannon N. Hardwick ◽  
Marina Snellings ◽  
Brian C. Ferslew ◽  
Yang Lu ◽  
Kim L.R. Browuer
Keyword(s):  
Breast Cancer ◽  
Multidrug Resistance ◽  
Abc Transporters ◽  
Breast Cancer Resistance Protein ◽  
Kinase Inhibitors ◽  
Efflux Transporters ◽  
Atp Binding ◽  
Cancer Resistance ◽  
Sulfate Uptake ◽  
Resistance Protein

<p class="PaperKeywordTitle">Tyrosine and aurora kinases are important effectors in signal transduction pathways that are often involved in aberrant cancer cell growth. Tyrosine (TKI) and aurora (AKI) kinase inhibitors are anti-cancer agents specifically designed to target such signaling pathways through TKI/AKI binding to the ATP-binding pocket of kinases thereby leading to diminished kinase activity. Some TKIs have been identified as inhibitors of ATP-binding cassette (ABC) transporters such as P-glycoprotein and breast cancer resistance protein (BCRP), which are commonly upregulated in malignant cells. TKI/AKIs have been investigated as ABC transporter inhibitors in order to facilitate the accumulation of concomitantly administered chemo-therapeutics within cancer cells. However, ABC transporters are prominently expressed in the liver and other eliminating organs, and their inhibition has been linked to intracellular accumulation of drugs, altered disposition, and toxicity. The potential for TKIs/AKIs to inhibit other important hepatic efflux transporters, particularly multidrug resistance-associated proteins (MRPs), remains unknown. The aim of the current study was to compare the inhibitory potency of 20 selected TKI/AKIs against MRP4 and BCRP through the use of inverted membrane vesicle assays. Relative IC<sub>50 </sub>values were estimated by determining TKI/AKI inhibition of MRP4-mediated [<sup>3</sup>H]-dehydroepiandrosterone sulfate uptake and BCRP-mediated [<sup>3</sup>H]-estrone sulfate uptake. To provide insight to the clinical relevance of TKI/AKI inhibition of ABC efflux transporters, the ratio of the steady-state maximum total plasma concentration (C<sub>ss</sub>) to the IC<sub>50</sub> for each compound was calculated with C<sub>ss</sub>/IC<sub>50</sub> ratio &gt;0.1 deemed potentially clinically relevant. Such analysis identified several potentially clinically relevant inhibitors of MRP4: alisertib, danusertib, erlotinib, lapatinib, neratinib, nilotinib, pazopanib, sorafenib, and tozasertib. The potentially clinically relevant inhibition of BCRP was much more extensive and included alisertib, barasertib, danusertib, enzastaurin, erlotinib, gefitinib, imatinib, neratinib, nilotinib, pazopanib, selumetinib, sorafenib, sunitinib, tozasertib, and vandetanib. These findings indicate the significant potential for TKI/AKIs to inhibit multiple ABC efflux transporters. The resulting inhibition data could provide insight regarding the clinical interpretation of pharmacokinetic/pharmacodynamic outcomes when TKI/AKIs are administered concomitantly with additional chemotherapeutic agents.</p>

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