國家衛生研究院 NHRI:Item 3990099045/15187

NHRI > Institute of Biotechnology and Pharmaceutical Research > Jinq-Chyi Lee > Periodical Articles > Item 3990099045/15187

Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/15187

Title:	Discovery of tetrasubstituted thiophenes as Cisd2 activators: A potential novel therapeutic option in nonalcoholic fatty liver disease
Authors:	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
Contributors:	Institute of Biotechnology and Pharmaceutical Research;Institute of Molecular and Genomic Medicine
Abstract:	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.
Date:	2023-10-05
Relation:	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
Appears in Collections:	[Jinq-Chyi Lee] Periodical Articles [Teng-Kuang Yeh] Periodical Articles [Others] Periodical Articles

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