相关实验视频

Updated: Jan 14, 2026

Author Spotlight: Establishing MASLD Cell Models for Investigating Disease Mechanisms and the Lipid-Lowering Effects of Koumiss

Author Spotlight: Establishing MASLD Cell Models for Investigating Disease Mechanisms and the Lipid-Lowering Effects of Koumiss

Published on: July 19, 2024

酸类型326E通过对ACLY和PPARα的双重向缓解了与代谢功能障碍相关的脂肪肝炎

Zhifu Xie¹, Long Cheng¹, Yue Hu²

¹State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, P.R. China; University of Chinese Academy of Sciences, Beijing 100049, P.R. China.

Cell metabolism

|October 23, 2025

概括

试验药物326E通过抑制ACLY和激活PPARα显著降低肝脂肪并减轻与代谢功能障碍相关的脂肪肝炎 (MASH),在临床前和临床研究中显示出有前途.

科学领域:

肝病学肝病学是一种肝病学.
药理学药理学是指药理学的学科.
代谢疾病代谢疾病

背景情况:

代谢功能障碍相关的脂肪肝炎 (MASH) 患病率正在上升,这是由受损的脂质代谢驱动的.
目前的MASH治疗方法有限,需要新的治疗策略.

研究的目的:

在临床前MASH模型中评估ATP-酸酶 (ACLY) 抑制剂326E的疗效.
阐明326E的双重作用机制,包括ACLY抑制和PPARα激活.
在MASH临床试验中评估326E的安全性和有效性.

主要方法:

在MASH的小鼠模型中评估了326E的疗效.
机理学研究涉及评估新的脂质生成 (DNL) 和脂肪酸氧化 (FAO) 途径.
在Cynomolgus子中进行了灵长类动物研究.
一个随机的1b/2a期临床试验 (NCT06491576) 在MASH患者中.

主要成果:

326E显著降低了肝脂积累,并在小鼠模型中缓解了MASH.
326E抑制了ACLY,降低了DNL,而全osterically激活的PPARα,增加了FAO.
由于ACLY的抑制抑制了粮农组织产品回收利用,提高了PPARα的有效性.
326E在Cynomolgus子中显示出有效性.
在MASH患者中,326E耐受性良好,并且减少了玛-氨基转移酶 (γ-GGT).

结论:

326E通过双重机制对MASH表现出治疗潜力.
该药物抑制ACLY并激活PPARα,解决关键的MASH病理.
326E是MASH的一种有前途的新型治疗候选药物.

关键词:

326E 是一个 326E 的类型.艾克利·阿克利 (aclyly) 是一个这是一种PPARα.脂肪酸β-氧化脂肪酸β-氧化脂质生成是指脂肪的产生.与代谢功能障碍相关的脂肪肝炎.第1b/2a期临床试验

更多相关视频

Optimized Analysis of In Vivo and In Vitro Hepatic Steatosis

Optimized Analysis of In Vivo and In Vitro Hepatic Steatosis

Published on: March 11, 2017

Inducing and Characterizing Vesicular Steatosis in Differentiated HepaRG Cells

Inducing and Characterizing Vesicular Steatosis in Differentiated HepaRG Cells

Published on: July 18, 2019

相关概念视频

Chronic Pancreatitis II: Collaborative Care

Chronic Pancreatitis II: Collaborative Care

The management of chronic pancreatitis is multifaceted, involving a comprehensive approach that includes thorough assessment, diagnostic testing, and a variety of management strategies.
Assessment:

Phase II Reactions: Acetylation Reactions

Phase II Reactions: Acetylation Reactions

Acetylation, a phase II biotransformation reaction, introduces an acetyl group to drugs or their metabolites. Acetyltransferase enzymes facilitate this reaction, which resembles α-amino acid conjugation due to the addition of a functional group to the drug molecule.
The substrates for acetylation are typically drugs or their metabolites with an amino, sulfonamide, or hydrazine functional group. Acetylation can occur at several points in the drug molecule, including primary, secondary, and...

Chronic Pancreatitis I: Introduction

Chronic Pancreatitis I: Introduction

The pancreas, an elongated and flat gland situated behind the stomach, serves a vital function in digesting food and managing blood sugar levels.
Pancreatitis is the inflammation of the pancreas, which occurs when the immune system becomes active and causes swelling, pain, and disruptions in organ function. Pancreatitis can manifest as either an acute or chronic condition.
Acute pancreatitis arises suddenly and lasts for a brief duration, while chronic pancreatitis is a long-term affliction...

Dipeptidyl Peptidase 4 Inhibitors

Dipeptidyl Peptidase 4 Inhibitors

Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a...

Overview of Fatty Acid Metabolism

Overview of Fatty Acid Metabolism

Lipids also are sources of energy that power cellular processes. Like carbohydrates, lipids are composed of carbon, hydrogen, and oxygen, but these atoms are arranged differently. Most lipids are nonpolar and hydrophobic. Major types include fats and oils, waxes, phospholipids, and steroids.
Fatty acids are catabolized in a process called beta-oxidation, which takes place in the matrix of the mitochondria and converts their fatty acid chains into two-carbon units of acetyl groups. The acetyl...

Lipid Catabolism

Lipid Catabolism

Triglycerides serve as crucial long-term energy storage molecules in microorganisms, providing a dense source of metabolic energy. Their breakdown is mediated by lipases, which hydrolyze triglycerides into glycerol and free fatty acids. Each of these components follows distinct metabolic pathways, ultimately contributing to ATP synthesis and cellular energy homeostasis.Glycerol MetabolismGlycerol, released from triglyceride hydrolysis, is phosphorylated by glycerol kinase to form...