SIMPLE AROMATICS IDENTIFIED WITH A NFAT-LACZ TRANSCRIPTION ASSAY FOR THE DETECTION OF IMMUNOSUPPRESSANTS

Determination of the mechanism of action of FK506 and cyclosporin A ha s yielded new molecular targets involved in signal transduction during T cell activation. A common target of FK506 and cyclosporin A is inhi bition of activation of the NFAT transcription factor, for which a spe cific binding region is present in the promoter of the IL-2 gene. A re porter gene assay has been used to screen for agents that interfere wi th this early step in T cell activation. Simple aromatic compounds tha t block NFAT-dependent transcription and show in vitro immunosuppressi ve activity were isolated from the broth and mycelia of two Streptomyc es sp. fermentations. The compounds were active at concentrations that were not directly cytotoxic.