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

Research output: Contribution to journalArticle

Authors

  • Roshni Malde
  • Rory C Mykura
  • Alfie T Baker
  • Cécile S. Le Duff

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.

Details

Original languageEnglish
Pages (from-to)2111-2117
JournalJournal of Medicinal Chemistry
Volume61
Issue number5
Publication statusPublished - 19 Feb 2018