Abstract
The aryloxy triester phosphoramidate prodrug approach has been used with success in drug discovery. Herein, we describe the first application of this prodrug technology to the monophosphate derivative of the phosphoantigen HMBPP and one of its analogues. Some of these prodrugs exhibited specific and potent activation of Vγ9/Vδ2 T-cells, which were then able to lyse bladder cancer cells in vitro. This work highlights the promise of this prodrug technology in the discovery of novel immunotherapeutics.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amides / chemical synthesis*
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Amides / pharmacology
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Cells, Cultured
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Humans
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Immunotherapy / methods
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Lymphocyte Activation / drug effects
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Organophosphates / chemistry
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Phosphoric Acids / chemical synthesis*
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Phosphoric Acids / pharmacology
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Prodrugs / chemical synthesis*
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Prodrugs / pharmacology
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Receptors, Antigen, T-Cell, gamma-delta / immunology
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T-Cell Antigen Receptor Specificity
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T-Lymphocyte Subsets / immunology*
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Urinary Bladder Neoplasms / therapy
Substances
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4-hydroxy-3-methyl-2-butenyl diphosphate
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Amides
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Organophosphates
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Phosphoric Acids
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Prodrugs
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Receptors, Antigen, T-Cell, gamma-delta
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phosphoramidic acid