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• W1985087178 abstract "The purpose of this work was to introduce a chemical modification into the paclitaxel (Taxol) structure to reduce interactions with the product of the multidrug resistant type 1 (MDR1) gene, P-glycoprotein (Pgp), resulting in improved blood−brain barrier (BBB) permeability. Specifically, a taxane analogue, Tx-67, with a succinate group added at the C10 position of Taxol, was synthesized and identified as such a candidate. In comparison studies, Tx-67 had no apparent interactions with Pgp, as demonstrated by the lack of enhanced uptake of rhodamine 123 by brain microvessel endothelial cells (BMECs) in the presence of the agent. By contrast, Taxol exposure substantially enhanced rhodamine 123 uptake by BMECs through inhibition of Pgp. The transport across BMEC monolayers was polarized for both Tx-67 and Taxol with permeation in the apical to basolateral direction greater for Tx-67 and substantially reduced for Taxol relative to basolateral to apical permeation. Taxol and cyclosporin A treatments also did not enhance Tx-67 permeation across BMEC monolayers. In an in situ rat brain perfusion study, Tx-67 was demonstrated to permeate across the BBB at a greater rate than Taxol. These results demonstrate that the Taxol analogue Tx-67 had a reduced interaction with Pgp and, as a consequence, enhanced permeation across the blood−brain barrier in vitro and in situ." @default.
• W1985087178 created "2016-06-24" @default.
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• W1985087178 date "2005-01-05" @default.
• W1985087178 modified "2023-09-23" @default.
• W1985087178 title "Chemical Modification of Paclitaxel (Taxol) Reduces P-Glycoprotein Interactions and Increases Permeation across the Blood−Brain Barrier in Vitro and in Situ" @default.
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• W1985087178 doi "https://doi.org/10.1021/jm040114b" @default.
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