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Synthesis and biological evaluation of (E)-4-hydroxy-3-methylbut2-enyl phosphate (HMBP) aryloxy triester phosphoramidate Prdrugs as activators of Vγ9/Vδ2 T-cells immune response

Davey, Martin S., Malde, Roshni, Mykura, Rory C., Baker, Alfie T., Taher, Taher E., Le Duff, Cécile S., Willcox, Benjamin E. and Mehellou, Youcef 2018. Synthesis and biological evaluation of (E)-4-hydroxy-3-methylbut2-enyl phosphate (HMBP) aryloxy triester phosphoramidate Prdrugs as activators of Vγ9/Vδ2 T-cells immune response. Journal of Medicinal Chemistry 61 (5) , pp. 2111-2117. 10.1021/acs.jmedchem.7b01824

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Pharmacy
Publisher: American Chemical Society
ISSN: 0022-2623
Date of First Compliant Deposit: 21 February 2018
Date of Acceptance: 19 February 2018
Last Modified: 15 Apr 2019 08:59
URI: http://orca.cf.ac.uk/id/eprint/109366

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