Format

Send to:

Choose Destination
See comment in PubMed Commons below
J Antibiot (Tokyo). 2008 Aug;61(8):496-502. doi: 10.1038/ja.2008.66.

New eremophilane sesquiterpenoid compounds, eremoxylarins A and B directly inhibit calcineurin in a manner independent of immunophilin.

Author information

  • 1Laboratory of Chemical Biology, Faculty of Agriculture, Iwate University, Iwate, Japan. kimurak@iwate-u.ac.jp

Abstract

In the course of our screening program for a new Ca2+-signal transduction inhibitor using the hypersensitive mutant strain of Saccharomyces cerevisiae (zds1Delta erg3Delta pdr1Delta pdr3Delta), new eremophilane sesquiterpenoid compounds eremoxylarins A and B were found to restore the growth inhibition caused by the hyperactivated Ca2+-signal. These compounds showed lethal activity against the mpk1Delta strain, specifically, compared to the cnb1Delta strain, and ion-sensitive activity against the wild-type strain in the presence of LiCl, indicating that their molecular target might be the calcineurin pathway. They inhibited calcineurin directly without immunophilins at IC50=2.7 and 1.4 microM with competitive inhibition in vitro. The eremophilane sesquiterpenoid structure in eremoxylarins could be a good leading compound for immunosuppressants and anti-allergy drugs.

PMID:
18997388
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group
    Loading ...
    Write to the Help Desk