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• W2170733312 endingPage "632" @default.
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• W2170733312 abstract "Organic anion-transporting polypeptides 1B1 and 1B3 (OATP1B1 and OATP1B3) are liver-specific transporters that mediate the uptake of a broad range of drugs into hepatocytes, including statins, antibiotics, and many anticancer drugs. Compounds that alter transport by one or both of these OATPs could potentially be used to target drugs to hepatocytes or improve the bioavailability of drugs that are cleared by the liver. In this study, we applied a bioassay-guided isolation approach to identify such compounds from the organic extract of <i>Rollinia emarginata</i> Schlecht (Annonaceae). Fractions of the plant extract were screened for effects on OATP1B1- and OATP1B3-mediated transport of the model substrates estradiol-17β-glucuronide and estrone-3-sulfate. We isolated three compounds, ursolic acid, oleanolic acid, and 8-<i>trans-p</i>-coumaroyloxy-α-terpineol, which inhibited estradiol-17β-glucuronide uptake by OATP1B1 but not OATP1B3. In addition, a rare compound, quercetin 3-<i>O</i>-α-l-arabinopyranosyl(1→2) α-l-rhamnopyranoside, was identified that had distinct effects on each OATP. OATP1B1 was strongly inhibited, as was OATP1B3-mediated transport of estradiol-17β-glucuronide. However, OATP1B3-mediated uptake of estrone-3-sulfate was stimulated 4- to 5-fold. Kinetic analysis of this stimulation revealed that the apparent affinity for estrone-3-sulfate was increased (decreased <i>K</i>_m), whereas the maximal rate of transport (<i>V</i>_max) was significantly reduced. These results demonstrate a mechanism through which the hepatic uptake of drug OATP substrates could be stimulated." @default.
• W2170733312 created "2016-06-24" @default.
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• W2170733312 date "2011-08-16" @default.
• W2170733312 modified "2023-09-27" @default.
• W2170733312 title "Isolation of Modulators of the Liver-Specific Organic Anion-Transporting Polypeptides (OATPs) 1B1 and 1B3 from <i>Rollinia emarginata</i> Schlecht (Annonaceae)" @default.
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• W2170733312 doi "https://doi.org/10.1124/jpet.111.184564" @default.
• W2170733312 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3199999" @default.
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• W2170733312 hasPublicationYear "2011" @default.
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