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

Erkel, G; Rether, J; Anke, T and Sterner, Olov LU (2003) In Journal of Antibiotics 56(4). p.337-343
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Antibiotics
volume
56
issue
4
pages
337 - 343
publisher
Japan Antibiotics Research Association
external identifiers
  • wos:000182565800001
  • pmid:12817806
  • scopus:0037959568
ISSN
0021-8820
language
English
LU publication?
yes
id
8ea5ee20-9a8e-427a-83a4-eb91045fc6ca (old id 127921)
alternative location
http://www.antibiotics.or.jp/journal/contents/vol-56/abstract/56-4/ja560401.htm
http://www.antibiotics.or.jp/journal/contents/vol-56/56contents_1.htm#febraury
date added to LUP
2007-07-10 09:47:49
date last changed
2017-08-06 04:26:24
@article{8ea5ee20-9a8e-427a-83a4-eb91045fc6ca,
  abstract     = {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.},
  author       = {Erkel, G and Rether, J and Anke, T and Sterner, Olov},
  issn         = {0021-8820},
  language     = {eng},
  number       = {4},
  pages        = {337--343},
  publisher    = {Japan Antibiotics Research Association},
  series       = {Journal of Antibiotics},
  title        = {S14-95, a novel inhibitor of the JAK/STAT pathway from a Penicillium species.},
  volume       = {56},
  year         = {2003},
}