3-(13-hydroxytridecyl)-1-[13-(3-pyridyl)tridecyl] pyridinium chloride (YM-53792), a novel inhibitor of NF-AT activation

A compound, YM-53792, was identified as an inhibitor of interleukin-2 (IL-2) gene promoter activity, using a Jurkat cell based reporter system in which the luciferase gene is regulated by the IL-2 gene promoter. Production of IL-2, interleukin-4 (IL-4) and interleukin-5 (IL-5) from human peripheral blood mononuclear cells was suppressed by YM-53792 in a dose-dependent fashion. Since expression of these cytokine genes is known to be regulated by NF-AT, we examined whether the promoter activity created by multimerization of NF-AT elements was inhibited with YM-53792. YM-53792 inhibited this promoter activity, but not AP-1- and NF-kappa B-driven promoter activities nor SV40 enhancer/promoter activity. In addition, electrophoretic mobility shift assays did not detect NF-AT/DNA complexes when nuclear extract prepared from YM-53792-treated, PMA/A23187-stimulated Jurkat cells was used, whereas AP-1/DNA complexes were observed. These results suggest that YM-53792 specifically inhibits the activation of NF-AT. (C) 1997 Elsevier Science Inc.