Letters in Drug Design & Discovery

G. Perry
University of Texas
San Antonio, TX
Email: lddd@benthamscience.org


Chemogenomic Investigation of AP-1 Transcriptional Regulation of LTC4 Synthase Expression

Author(s): Tiana Chong, Michael McMillan, Jia Ling Teo, William R. Henderson Jr., Michael Kahn.


Asthma has reached epidemic proportions with approximately 200 million individuals affected worldwide. The disease is characterized by an oxidant / antioxidant imbalance in the lungs leading to activation of redox-sensitive transcription factors e.g. activator protein 1 (AP-1) and nuclear factor kappa B (NF-kappa B). We have previously described PNRI-299, a small molecule beta-strand mimetic template compound, as an inhibitor of the multifunctional AP endonuclease / redox factor 1 (Ref-1) [1]. PNRI-299 has demonstrable effects on the reduction of AP-1 driven transcription and beneficial pharmacological effects in a mouse asthma model. We now report the synthesis of this molecule and the effects of PNRI-299 on the expression of Leukotriene C4 (LTC4) synthase, a crucial enzyme for the formation of the cysteinyl leukotrienes.

Keywords: ap-1 transcriptional regulation, redox-sensitive transcription factors, activator protein 1

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Article Details

Year: 2004
Page: [211 - 216]
Pages: 6
DOI: 10.2174/1570180043398920
Price: $58