一种口服,肝脏受限的LXR逆agonist用于失脂症:临床前发展和第一阶段试验
Xiaoxu Li1, Giorgia Benegiamo1, Archana Vijayakumar2
1Laboratory of Integrative Systems Physiology, Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Nature medicine
|January 16, 2026
概括
肝X受体 (LXR) 反向激动剂,如TLC-2716,通过向富含甘油三酸的脂蛋白,显示出对治疗脱脂症和降低心血管疾病风险的承诺.
科学领域:
- 生物化学 生物化学
- 药理学 药理学是指药理学的学科.
- 心血管医学 心血管医学
背景情况:
- 动脉样性心血管疾病 (ASCVD) 仍然是导致死亡的主要原因,尽管目前的治疗方法.
- 与失脂症相关的残留风险需要新的治疗策略.
- 向富含甘油三 (TG) 的脂蛋白为管理ASCVD提供了一个有前途的方法.
研究的目的:
- 研究肝X受体 (LXR) 逆agonists在脂质代谢和代谢疾病中的作用.
- 在临床前模型和人体试验中评估TLC-2716,一种肠道和肝脏受限制的LXR逆agonist的安全性和有效性.
- 评估TLC-2716在治疗脱脂症和降低残留ASCVD风险方面的潜力.
主要方法:
- 利用人类肝脏器官来模拟脂肪肝炎,并评估TLC-2716对脂质积累,炎症和纤维化的影响.
- 进行了随机的,安慰剂控制的第一阶段临床试验,以评估TLC-2716的耐受性和对脂质资料的影响.
- 口服TLC-2716作为肠道和肝脏受限制的LXR逆agonist.
主要成果:
- TLC-2716在人类肝脏有机体中显示减少了脂质积累,炎症和纤维化基因表达.
- 第1期试验显示,TLC-2716在14天内耐受良好.
- 观察到与安慰剂调整后的血TG降低高达38.5%,食后残留胆固醇降低61%.
结论:
- 在人类中,TLC-2716表现出良好的耐受性和显著的降脂效应.
- 这种LXR逆agonist代表了一种潜在的治疗药物用于失脂症和残留ASCVD风险.
- 进一步的临床开发TLC-2716是有必要的管理代谢性疾病.
相关概念视频
01:20Lipid-Lowering Drugs: Statins and Miscellaneous Agents
1.3K
Hyperlipidemia, a medical condition often referred to as high cholesterol, is characterized by abnormally elevated levels of lipids in the bloodstream. When present in excess, these lipids, specifically cholesterol and triglycerides, can lead to serious health complications, often involving cardiovascular diseases. Illnesses like atherosclerosis, heart attacks, and pancreatitis have all been linked to untreated hyperlipidemia. This means controlling and regulating cholesterol and triglyceride...
1.3K
01:24Lipid Absorption
2.5K
Dietary triglycerides from chyme in the duodenum are mixed with bile salts produced by the liver to emulsify fats. As a result, large droplets are broken down into smaller ones, increasing the surface area for enzymatic action. Once emulsified, pancreatic lipases hydrolyze the triglycerides into free fatty acids and monoglycerides.
These breakdown products bind with bile salts and lecithin to form micelles, which quickly pass between microvilli to come in close contact with the apical...
These breakdown products bind with bile salts and lecithin to form micelles, which quickly pass between microvilli to come in close contact with the apical...
2.5K
01:30Liver Physiology
3.5K
The liver, an essential organ in the human body, performs over 200 vital functions that can be broadly categorized into metabolic, hematological, endocrine regulation, and bile production.
Metabolic Regulation:
The liver is the central organ involved in regulating blood composition. It stabilizes blood glucose levels, maintaining them within the range of 70–110 mg/dL. When these levels drop, the liver breaks down glycogen reserves and releases glucose into the bloodstream. It can...
Metabolic Regulation:
The liver is the central organ involved in regulating blood composition. It stabilizes blood glucose levels, maintaining them within the range of 70–110 mg/dL. When these levels drop, the liver breaks down glycogen reserves and releases glucose into the bloodstream. It can...
3.5K
01:06Lipid Digestion
98.8K
Lipids are large molecules that are generally not water-soluble. Since most of the digestive enzymes in the human body are water-based, there are specific steps the body must take to break down lipids and make them available for use.
98.8K