Treatment of Sepsis Pathogenesis with High Mobility Group Box Protein 1­Regulating Anti-inflammatory Agents

Title
Treatment of Sepsis Pathogenesis with High Mobility Group Box Protein 1­Regulating Anti-inflammatory Agents
Authors
이상희조완상구자영박연주오근희송진숙배명애임동현이동섭박승범
Issue Date
2017-01
Publisher
Journal of medicinal chemistry
Citation
VOL 60, NO 1-179
Abstract
Sepsis is one of the major causes of death worldwide when associated with multiple organ failure. However, there is a critical lack of adequate sepsis therapies because of its diverse patterns of pathogenesis. The pro-inflammatory cytokine cascade mediates sepsis pathogenesis, and high mobility group box proteins (HMGBs) play an important role as late-stage cytokines. We previously reported the small-molecule modulator, inflachromene (1d), which inhibits the release of HMGBs and, thereby, reduces the production of pro-inflammatory cytokines. In this context, we intraperitoneally administered Id to a cecal ligation and puncture (CLP)-induced mouse model of sepsis and confirmed that it successfully ameliorated sepsis pathogenesis. On the basis of a structure activity relationship study, we discovered new candidate compounds, 2j and 21, with improved therapeutic efficacy in vivo. Therefore, our study clearly demonstrates that the regulation of HMGB1 release using small molecules is a promising strategy for the treatment of sepsis.
URI
http://pubs.kist.re.kr/handle/201004/67448
ISSN
0022-2623
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KIST Publication > Article
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