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,Journal of Medicinal Chemistry

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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
Journal of Medicinal Chemistry ( IF 6.8 ) Pub Date : 2018-02-19 00:00:00 , DOI: 10.1021/acs.jmedchem.7b01824
Martin S. Davey , Roshni Malde , Rory C. Mykura , Alfie T. Baker , Taher E. Taher , Cécile S. Le Duff , Benjamin E. Willcox , Youcef Mehellou ₁

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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.

中文翻译：

（E）-4-羟基-3-甲基丁-2-烯基磷酸酯（HMBP）芳氧基三酯磷酸氨基甲酸酯前药的合成及生物学评价

芳氧基三酯氨基磷酸酯前药方法已成功用于药物发现中。在这里，我们描述了这种前药技术在磷酸抗原HMBPP的单磷酸酯衍生物及其类似物中的首次应用。这些前药中的一些表现出Vγ9/Vδ2T细胞的特异性和有效激活，然后能够体外裂解膀胱癌细胞。这项工作凸显了这种前药技术在发现新型免疫疗法中的前景。

更新日期：2018-02-19

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