國家衛生研究院 NHRI:Item 3990099045/15187
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    题名: Discovery of tetrasubstituted thiophenes as Cisd2 activators: A potential novel therapeutic option in nonalcoholic fatty liver disease
    作者: Yao, CH;Shen, ZQ;Rajan, YC;Huang, YW;Lin, CY;Song, JS;Shiao, HY;Ke, YY;Fan, YS;Tsai, CH;Yeh, TK;Tsai, TF;Lee, JC
    贡献者: Institute of Biotechnology and Pharmaceutical Research;Institute of Molecular and Genomic Medicine
    摘要: Down-regulation of Cisd2 in the liver has been implicated in the development of nonalcoholic fatty liver disease (NAFLD) and increasing the level of Cisd2 is therefore a potential therapeutic approach to this group of diseases. Herein, we describe the design, synthesis, and biological evaluation of a series of Cisd2 activators, all thiophene analogs, based on a hit obtained using two-stage screening and prepared via either the Gewald reaction or by intramolecular aldol-type condensation of an N,S-acetal. Metabolic stability studies of the resulting potent Cisd2 activators suggest that thiophenes 4q and 6 are suitable for in vivo studies. The results from studies on 4q-treated and 6-treated Cisd2hKO-het mice, which carry a heterozygous hepatocyte-specific Cisd2 knockout, confirm that (1) there is a correlation between Cisd2 levels and NAFLD and (2) these compounds have the ability to prevent, without detectable toxicity, the development and progression of NAFLD.
    日期: 2023-10-05
    關聯: European Journal of Medicinal Chemistry. 2023 Oct 05;258:Article number 115583.
    Link to: http://dx.doi.org/10.1016/j.ejmech.2023.115583
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0223-5234&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:001032419800001
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85163882292
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