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Letters in Drug Design & Discovery


ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

Interaction of Probenecid with the Breast Cancer Resistance Protein Transporter (BCRP/ABCG2)

Author(s): G. Merino, R. Real, A. J. Molina, M. M. Pulido, J. G. Prieto and A. I. Alvarez

Volume 3, Issue 4, 2006

Page: [236 - 241] Pages: 6

DOI: 10.2174/157018006776743170

Price: $65


Probenecid is used as a uricosuric agent in the treatment of chronic gout and as an adjunct to enhance antibiotic levels in the blood. For research purposes, it is used as a prototypic inhibitor of organic anion transporters and MRPs, including MPR2. The purpose of this research is to study the interaction of probenecid with two other important transporters of the ATP-binding cassette family, Breast Cancer Resistance Protein (BCRP) and P-glycoprotein. These drug efflux transporters are present in the intestine, liver and other organs, and they affect the bioavailability of many compounds. Using the polarized canine kidney cell line MDCK-II and its human MDR1-, BCRP- and murine Bcrp1-transduced subclones, we found that probenecid is transported by mouse Bcrp1 and human BCRP, but not by P-glycoprotein. In addition, flow cytometry experiments showed that probenecid did not affect the accumulation of mitoxantrone in Bcrp1- and BCRPtransduced cells, indicating that this compound was not an effective BCRP/Bcrp1 inhibitor at the concentrations used. We conclude that probenecid is a good substrate of BCRP/Bcrp1, suggesting potential interaction with BCRP/Bcrp1 inhibitors.

Keywords: Probenecid, Breast Cancer Resistance Protein, P-glycoprotein, transport, inhibition

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