6533b862fe1ef96bd12c6525

RESEARCH PRODUCT

Oxacyclododecindione, a Novel Inhibitor of IL-4 Signaling from Exserohilum rostratum

Gerhard ErkelTimm AnkeTill OpatzJohannes C. LiermannHorst KunzHeinz KolshornAnnegret SerweHanane Belahmer

subject

Spectrometry Mass Electrospray IonizationMacrocyclic CompoundsMagnetic Resonance Spectroscopyfood.ingredientBlotting WesternGene ExpressionBiologyTransfectionStructure-Activity Relationshipchemistry.chemical_compoundfoodCell Line TumorDrug DiscoveryHumansTranscription factorSTAT6PharmacologyReporter geneTyrosine phosphorylationTransfectionMolecular biologyExserohilumDNA binding sitechemistryBiochemistryFermentationInterleukin-4Mitosporic FungiSignal transductionSTAT6 Transcription FactorSignal Transduction

description

In a screening program for new metabolites from fungi inhibiting the IL-4 mediated signal transduction, a novel chlorinated macrocyclic lactone, designated as oxacyclododecindione, was isolated from fermentations of the imperfect fungus Exserohilum rostratum. The structure was determined by a combination of spectroscopic techniques. Oxacyclododecindione inhibits the IL-4 induced expression of the reporter gene secreted alkaline phosphatase (SEAP) in transiently transfected HepG2 cells with IC50 values of 20-25 ng/ml (54-67.5 nM). Studies on the mode of action of the compound revealed that the inhibition of the IL-4 dependent signaling pathway is caused by blocking the binding of the activated STAT6 transcription factors to the DNA binding site without inhibiting tyrosine phosphorylation. The compound has no antibacterial or antifungal activity.

yearjournalcountryeditionlanguage
2008-07-26The Journal of Antibiotics
https://doi.org/10.1038/ja.2008.40