کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2485158 | 1114346 | 2012 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Differential Selectivity of Efflux Transporter Inhibitors in Caco-2 and MDCK-MDR1 Monolayers: A Strategy to Assess the Interaction of a New Chemical Entity with P-gp, BCRP, and MRP2
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کلمات کلیدی
P-glycoprotein - P-گلیکوپروتئینIntestinal absorption - جذب رودهTransporters - حمل و نقلActive transport - حمل و نقل فعالABC transporters - حمل کننده ABCMembrane transporter - حمل کننده غشاییMultidrug resistance transporters - حمل کننده های مقاوم در برابر چندین رژیمCaco-2 cells - سلول های Caco-2MDCK cells - سلول های MDCKIn vitro models - مدل های in vitro
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Differential Selectivity of Efflux Transporter Inhibitors in Caco-2 and MDCK-MDR1 Monolayers: A Strategy to Assess the Interaction of a New Chemical Entity with P-gp, BCRP, and MRP2 Differential Selectivity of Efflux Transporter Inhibitors in Caco-2 and MDCK-MDR1 Monolayers: A Strategy to Assess the Interaction of a New Chemical Entity with P-gp, BCRP, and MRP2](/preview/png/2485158.png)
چکیده انگلیسی
Determining the interaction of a molecule with membrane transporters is challenging because of overlapping substrate and inhibitor specificities and coexpression of multiple transporters. Caco-2 and MDCK-MDR1 cells were used to evaluate the selectivity of zosuquidar (LY335979), fumitremorgin C (FTC), and MK571 as inhibitors of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and multidrug resistance-associated protein 2 (MRP2), respectively. Although these compounds are commonly used as transporter inhibitors, the concentrations at which they selectively inhibit P-gp, BCRP, and MRP2 have not been definitively assessed. In Caco-2 cells, which express P-gp, BCRP, and MRP2, FTC (1 µM) selectively inhibited the efflux of BCRP substrates estrone-3-sulfate and genistein; however, at 10 µM, FTC partially inhibited the efflux of P-gp substrates paclitaxel and digoxin. MK571 (50 µM), commonly used to inhibit MRP2, inhibited the efflux of P-gp and BCRP probe substrates in Caco-2 cells. In MDCK-MDR1 cells, which express human P-gp but not BCRP or MRP2, MK571 (50 µM) and FTC (10 µM) did not inhibit paclitaxel and digoxin efflux. Using Caco-2 cell monolayers, selected probe substrates, and optimized concentrations of LY335979 (3 µM) and FTC (1 µM), we propose a strategy to evaluate the interaction of a molecule with P-gp, BCRP, and MRP2. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:1888-1897, 2012
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 101, Issue 5, May 2012, Pages 1888-1897
Journal: Journal of Pharmaceutical Sciences - Volume 101, Issue 5, May 2012, Pages 1888-1897
نویسندگان
Kirsten Mease, Rucha Sane, Lalitha Podila, Mitchell E. Taub,