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Biol Pharm Bull. 2012;35(5):805-9.

Tributylhexadecylphosphonium bromide, a novel nuclear factor of activated T cells signaling inhibitor, blocks interleukin-2 induction associated with inhibition of p70 ribosomal protein S6 kinase phosphorylation.

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  • 1Graduate School of Pharmaceutical Sciences, University of Shizuoka, Japan.


Transcriptional factors of the nuclear factor of activated T cells (NFAT) family are involved in T cell signaling. Many NFAT signaling inhibitors, such as cyclosporin A (CsA) and tacrolimus, abrogate dephosphorylation of NFAT proteins by inhibiting calcineurin activity. In pursuit of a novel type of NFAT signaling inhibitor, we screened our chemical library using the NFAT-dependent reporter assay and identified tributylhexadecylphosphonium bromide (THPB) as a selective NFAT signaling inhibitor. THPB inhibited NFAT-dependent reporter activity, and the induction of interleukin-2 (IL-2) at both mRNA and protein levels by calcium stimulation. Moreover, THPB had an additive effect on the inhibition of IL-2 induction with CsA. Unlike CsA, THPB did not affect dephosphorylation of NFAT1, but suppressed phosphorylation of p70 ribosomal protein S6 kinase (p70S6K). These results suggest that THPB may be a novel type of NFAT signaling inhibitor that acts in association with inhibition of p70S6K phosphorylation.

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