Abstract
We report the synthesis and blood-brain barrier (BBB)-permeability of (14)C-CNDR-29, a paclitaxel C-10 carbamate derivative shown to be devoid of P-glycoprotein (Pgp)-interactions, in an in situ mouse brain perfusion model, in comparison with (14)C-paclitaxel. The results presented reveal a 3- to 4-fold higher BBB-permeability for the C-10 modified taxane compared to paclitaxel. These results support the notion that circumvention of Pgp-mediated efflux can lead to higher BBB-permeability. Further studies however are needed to evaluate the therapeutic potential of the C-10 carbamates paclitaxel derivatives for the treatment of CNS diseases.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
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Animals
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Blood-Brain Barrier / drug effects*
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Brain / drug effects
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Carbamates* / chemical synthesis
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Carbamates* / chemistry
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Carbamates* / pharmacology
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Central Nervous System / metabolism
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Disease Models, Animal
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Mice
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Molecular Structure
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Neurodegenerative Diseases / drug therapy
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Paclitaxel / analogs & derivatives*
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Paclitaxel / chemical synthesis
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Paclitaxel / chemistry
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Paclitaxel / pharmacology
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Permeability
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Structure-Activity Relationship
Substances
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(14)C-CNDR-29
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ATP Binding Cassette Transporter, Subfamily B, Member 1
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Carbamates
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Paclitaxel