APC0576: a novel small molecule, immunosuppressive agent effective in primate models.

Background: APC0576, 5-(((S)-2,2-dimethylcyclopropanecarbonyl)amino)-2-(4-(((S)-2,2-dimethylcyclopropanecarbonyl)amino)phenoxy)pyridine is a novel synthetic compound with an inhibitory activity on NF-kappaB-dependent gene activation and chemokine synthesis in human endothelial cells. This article describes the effect of APC0576 on T-cell-dependent immune functions in vitro and in vivo in primate models, because NF-kappaB is known to be one of the potent mediators in T-cell activation.

Methods: The effects of APC0576 on interleukin-2 production and proliferative responses in human peripheral blood mononuclear cells were studied under various stimuli with in vitro culture assay.

APC0576, a novel inhibitor of NF-kappaB-dependent gene activation, prevents pro-inflammatory cytokine-induced chemokine production in human endothelial cells.

Endothelial cells participate in the inflammatory and immune reactions. Endothelial cell activation is a recurrent phenomenon linked to the pathogenesis of diverse human diseases, such as acute and chronic inflammation and cardiovascular disorders. Pro-inflammatory cytokines (e.