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S14-95, a novel inhibitor of the JAK/STAT pathway from a Penicillium species.

Author:
  • G Erkel
  • J Rether
  • T Anke
  • Olov Sterner
Publishing year: 2003
Language: English
Pages: 337-343
Publication/Series: Journal of Antibiotics
Volume: 56
Issue: 4
Document type: Journal article
Publisher: Japan Antibiotics Research Association

Abstract english

In a search for new inhibitors of the IFN-γ mediated signal transduction in HeLa S3 cells using secreted alkaline phosphatase (SEAP) as reporter gene, a novel compound, designated as S14-95 was isolated from fermentations of the imperfect fungus Penicillium sp. 14-95. The compound inhibits the IFN-γ mediated expression of the reporter gene with IC50 values of 2.5~5μg/ml (5.4~10.8μM). Furthermore the compound inhibited the expression of the proinflammatory enzymes COX-2 and NOS II at 5μg/ml (10.8μM) in LPS/IFN-γ stimulated J774 mouse macrophages. Studies on the mode of action of the compound revealed that the inhibition of the IFN-γ dependent signaling pathway is caused by an inhibition of the phosphorylation of the STAT1α transcription factor. In addition, S14-95 inhibited the activation of the p38 MAP kinase, which is involved in the inducible expression of many proinflammatory genes.

Keywords

  • Organic Chemistry

Other

Published
  • ISSN: 0021-8820
Olov Sterner
E-mail: olov [dot] sterner [at] science [dot] lu [dot] se

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Faculty of Science

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