PURPOSE: S-(4-Nitrobenzyl)-6-thioinosine (NBMPR) is routinely used at concentrations of 0.10 μM and 0.10 mM to specifically inhibit transport of nucleosides mediated by equilibrative nucleoside transporters 1 (ENT1) and 2 (ENT2), respectively. We recently showed that NBMPR (0.10 mM) might also inhibit placental active efflux of [3H]zidovudine and [3H]tenofovir disoproxil fumarate. Here we test the hypothesis that NBMPR abolishes the activity of P-glycoprotein (ABCB1) and/or breast cancer resistance protein (ABCG2). METHODS: We performed accumulation assays with Hoechst 33342 (a model dual substrate of ABCB1 and ABCG2) and bi-directional transport studies with the ABCG2 substrate [3H]glyburide in transduced MDCKII cells, accumulation studies in choriocarcinoma-derived BeWo cells, and in situ dual perfusions of rat term placenta with glyburide. RESULTS: NBMPR inhibited Hoechst 33342 accumulation in MDCKII-ABCG2 cells (IC50 = 53 μM) but not in MDCKII-ABCB1 and MDCKII-parental cells. NBMPR (0.10 mM) also inhibited bi-directional [3H]glyburide transport across monolayers of MDCKII-ABCG2 cells and blocked ABCG2-mediated [3H]glyburide efflux by rat term placenta in situ. CONCLUSION: NBMPR at a concentration of 0.10 mM abolishes ABCG2 activity. Researchers using NBMPR to evaluate the effect of ENTs on pharmacokinetics must therefore interpret their results carefully if studying compounds that are substrates of both ENTs and ABCG2.

• Keywords
• NBMPR, breast cancer resistance protein, equilibrative nucleoside transporters, inhibition, selectivity,
• MeSH
• ATP Binding Cassette Transporter, Subfamily G, Member 2 antagonists & inhibitors   metabolism   MeSH
• Antiviral Agents metabolism   pharmacokinetics   MeSH
• Biological Transport drug effects   MeSH
• Cell Line MeSH
• Madin Darby Canine Kidney Cells MeSH
• Rats MeSH
• Humans MeSH
• Neoplasm Proteins antagonists & inhibitors   metabolism   MeSH
• ATP Binding Cassette Transporter, Subfamily B antagonists & inhibitors   metabolism   MeSH
• Placenta drug effects   metabolism   MeSH
• Rats, Wistar MeSH
• Dogs MeSH
• Pregnancy MeSH
• Thioinosine analogs & derivatives   pharmacology   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Humans MeSH
• Dogs MeSH
• Pregnancy MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• 4-nitrobenzylthioinosine MeSH Browser
• ATP Binding Cassette Transporter, Subfamily G, Member 2 MeSH
• ABCB1 protein, human MeSH Browser
• ABCG2 protein, human MeSH Browser
• Antiviral Agents MeSH
• Neoplasm Proteins MeSH
• ATP Binding Cassette Transporter, Subfamily B MeSH
• Thioinosine MeSH