相关实验视频

Updated: Jan 15, 2026

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists

Published on: November 15, 2013

基于结构的新型核受体PPARγ抑制剂的发现:对肥胖和代谢疾病干预的含义

Phum Tachachartvanich¹, Rapeepat Sangsuwan², Nonticha Ngernpisutsilp³

¹Laboratory of Environmental Toxicology, Chulabhorn Research Institute, Bangkok 10210, Thailand; Environmental Toxicology Program, Chulabhorn Graduate Institute, Bangkok 10210, Thailand; Center of Excellence on Environmental Health and Toxicology (EHT), OPS, Ministry of Higher Education, Science, Research and Innovation, Bangkok, Thailand.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

|October 8, 2025

概括

一种新型化合物,化合物3,有效地抑制过氧体增殖器激活受体玛 (PPARγ),提供了一种有前途的新策略,通过抑制脂肪细胞发育来对抗肥胖和改善代谢健康.

科学领域:

分子生物学分子生物学
代谢障碍代谢障碍代谢障碍
药物发现药物发现药物发现

背景情况:

肥胖是一种由复杂的代谢失调驱动的全球健康危机.
氧酶增殖器激活受体玛 (PPARγ) 是脂肪细胞分化和新陈代谢的关键调节器,使其成为一个重要的治疗点.
抑制PPARγ活性是管理肥胖和相关代谢状况的未经探索的策略.

研究的目的:

通过基于结构的虚拟查来识别PPARγ的新型抑制剂.
在体外 (in vitro) 评估已识别的化合物的抗原性潜力.
阐明最强大的抑制剂的作用机制.

主要方法:

基于结构的多种化合物库 (>1000种化合物) 的虚拟选,以识别潜在的PPARγ抑制剂.
在试验室中对PPARγ点参与和在小鼠和人类脂肪细胞中的抗基因活性的顶级候选者的实验验证.
作用机制研究包括PPARγ交换活化试验,转录组分析和分子动力学模拟.

主要成果:

与已知的PPARγ抑制剂GW9662.2相比,化合物3显示出更强的抗原活性.
化合物3剂量依赖地抑制了PPARγ的交换活化,并降低了PPAR信号通路,脂肪细胞分化和脂质生成中的关键基因.
分子动力学模拟证实了PPARγ联体结合域内化合物3的稳定相互作用,支持其抑制功能.

结论:

化合物3被确定为一种强大的PPARγ抑制剂,具有显著的抗基效应.
这些发现突显了PPARγ抑制对肥胖和相关代谢障碍的治疗潜力.
该研究验证了核受体抑制作为向治疗策略.

关键词:

增脂生殖是一种增脂的过程.药物发现药物发现代谢性疾病是一种代谢性疾病.核受体是核受体中的一个.肥胖问题肥胖问题在PPARγ中,PPARγ是PPARγ

更多相关视频

Sample Preparation to Bioinformatics Analysis of DNA Methylation: Association Strategy for Obesity and Related Trait Studies

Sample Preparation to Bioinformatics Analysis of DNA Methylation: Association Strategy for Obesity and Related Trait Studies

Published on: May 6, 2022

Isolation and Differentiation of Stromal Vascular Cells to Beige/Brite Cells

Isolation and Differentiation of Stromal Vascular Cells to Beige/Brite Cells

Published on: March 28, 2013

相关概念视频

Transducer Mechanism: Nuclear Receptors

Transducer Mechanism: Nuclear Receptors

Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:

G Protein-coupled Receptors

G Protein-coupled Receptors

G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...