Design, synthesis, and biological evaluation of FXR/ASK1 dual-target modulators.

IF 2.7 4区化学 Q2 CHEMISTRY, ORGANIC

Beilstein Journal of Organic Chemistry Pub Date : 2026-05-20 eCollection Date: 2026-01-01 DOI:10.3762/bjoc.22.59

Xi Zhang, Jingyan Wang, Ziqiang Zhao, Caiyi Wang, Zenghui Ye, Wei-Yuan Ma, Jian-Xing Xu, Fengzhi Zhang

引用次数: 0

Abstract

The dual modulation of FXR and ASK1 is considered a promising therapeutic strategy for metabolic dysfunction-associated fatty liver disease (MAFLD) and its progressive form, metabolic dysfunction-associated steatohepatitis (MASH). GW4064 and GS-4997 are effective regulators for FXR and ASK1, respectively. Through the effective functional group splicing strategy, a new dual-target modulator is designed. Compound Z8, which acts on both targets, was found to more potently reduce intracellular lipid droplet accumulation in OA-treated HepG2 cells than the FXR agonist GW4064 and the ASK1 inhibitor selonsertib (GS-4997).

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FXR/ASK1双靶点调节剂的设计、合成及生物学评价

FXR和ASK1的双重调节被认为是治疗代谢功能障碍相关脂肪性肝病（MAFLD）及其进行性形式代谢功能障碍相关脂肪性肝炎（MASH）的一种有前景的治疗策略。GW4064和GS-4997分别是FXR和ASK1的有效调控因子。通过有效的官能团拼接策略，设计了一种新的双目标调制器。与FXR激动剂GW4064和ASK1抑制剂selonsertib （GS-4997）相比，化合物Z8可同时作用于这两个靶点，更有效地减少了经oa处理的HepG2细胞内脂滴的积累。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Beilstein Journal of Organic Chemistry 化学-有机化学

CiteScore

4.90

自引率

3.70%

发文量

167

审稿时长

1.4 months

期刊介绍： The Beilstein Journal of Organic Chemistry is an international, peer-reviewed, Open Access journal. It provides a unique platform for rapid publication without any charges (free for author and reader) – Platinum Open Access. The content is freely accessible 365 days a year to any user worldwide. Articles are available online immediately upon publication and are publicly archived in all major repositories. In addition, it provides a platform for publishing thematic issues (theme-based collections of articles) on topical issues in organic chemistry. The journal publishes high quality research and reviews in all areas of organic chemistry, including organic synthesis, organic reactions, natural product chemistry, structural investigations, supramolecular chemistry and chemical biology.