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Mixed Aryl Phosphonate Prodrugs of a Butyrophilin Ligand.

ABSTRACT: Studies of aryl phosphonate derivatives of a butyrophilin 3A1 ligand have resulted in identification of a potent stimulant of V?9 V?2 T cells. This compound, a mixed ester bearing one pivaloyloxymethyl substituent and one 1-naphthyl ester displayed an EC₅₀ of 0.79 nM as a stimulant of T cell proliferation, and a 9.0 nM EC₅₀ in an assay designed to measure interferon gamma production. In both assays, this is the most potent butyrophilin ligand prodrug yet reported, and thus it should be a valuable tool for studies of T cell function. Furthermore, mixed aryl/acyloxyalkyl esters may represent a new class of phosphonate prodrugs with high efficacy.

SUBMITTER: Foust BJ

PROVIDER: S-EPMC5601366 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Mixed Aryl Phosphonate Prodrugs of a Butyrophilin Ligand.

Foust Benjamin J BJ Poe Michael M MM Lentini Nicholas A NA Hsiao Chia-Hung Christine CC Wiemer Andrew J AJ Wiemer David F DF

ACS medicinal chemistry letters 20170809 9

Studies of aryl phosphonate derivatives of a butyrophilin 3A1 ligand have resulted in identification of a potent stimulant of Vγ9 Vδ2 T cells. This compound, a mixed ester bearing one pivaloyloxymethyl substituent and one 1-naphthyl ester displayed an EC<sub>50</sub> of 0.79 nM as a stimulant of T cell proliferation, and a 9.0 nM EC<sub>50</sub> in an assay designed to measure interferon gamma production. In both assays, this is the most potent butyrophilin ligand prodrug yet reported, and thus ...[more]

PMID: 28947936

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