Synthesis and Biological Evaluation of (E)-4-Hydroxy-3-methylbut-2-enyl Phosphate (HMBP) Aryloxy Triester Phosphoramidate Prodrugs as Activators of Vγ9/Vδ2 T-Cell Immune Responses

Martin S. Davey, Roshni Malde, Rory C. Mykura, Alfie T. Baker, Taher E. Taher, Cécile S. Le Duff, Benjamin E. Willcox, Youcef Mehellou

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12 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2111-2117
Number of pages7
JournalJournal of Medicinal Chemistry
Volume61
Issue number5
DOIs
Publication statusPublished - 8 Mar 2018
Externally publishedYes

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