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非酒精性脂肪性肝炎的潜在治疗策略:从临床前到临床开发

Potential therapeutic strategies for MASH: from preclinical to clinical development.

作者信息

Xie Zhifu, Li Yufeng, Cheng Long, Huang Yidan, Rao Wanglin, Shi Honglu, Li Jingya

机构信息

State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.

University of Chinese Academy of Sciences, Beijing 100049, China.

出版信息

Life Metab. 2024 Jul 6;3(5):loae029. doi: 10.1093/lifemeta/loae029. eCollection 2024 Oct.

Abstract

Current treatment paradigms for metabolic dysfunction-associated steatohepatitis (MASH) are based primarily on dietary restrictions and the use of existing drugs, including anti-diabetic and anti-obesity medications. Given the limited number of approved drugs specifically for MASH, recent efforts have focused on promising strategies that specifically target hepatic lipid metabolism, inflammation, fibrosis, or a combination of these processes. In this review, we examined the pathophysiology underlying the development of MASH in relation to recent advances in effective MASH therapy. Particularly, we analyzed the effects of lipogenesis inhibitors, nuclear receptor agonists, glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) agonists, fibroblast growth factor mimetics, and combinatorial therapeutic approaches. We summarize these targets along with their preclinical and clinical candidates with the ultimate goal of optimizing the therapeutic prospects for MASH.

摘要

代谢功能障碍相关脂肪性肝炎(MASH)的当前治疗模式主要基于饮食限制和现有药物的使用,包括抗糖尿病和抗肥胖药物。鉴于专门用于MASH的获批药物数量有限,最近的研究工作集中在针对肝脏脂质代谢、炎症、纤维化或这些过程组合的有前景的策略上。在这篇综述中,我们研究了与有效MASH治疗的最新进展相关的MASH发生发展的病理生理学。特别是,我们分析了脂肪生成抑制剂、核受体激动剂、胰高血糖素样肽-1(GLP-1)受体(GLP-1R)激动剂、成纤维细胞生长因子模拟物和联合治疗方法的作用。我们总结了这些靶点及其临床前和临床候选药物,最终目标是优化MASH的治疗前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d559/11749562/b5887ec7347b/loae029_fig1.jpg

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