通过联合虚拟查策略识别了一种针对Keap1的新型和高亲和度循环,用于治疗炎症
Shenglin Gao1,2, Xiaokai Shi1,2, Shudan Yang3
1Department of Urology, The third affiliated hospital of Nanjing medical university, Nanjing medical university, Changzhou, China.
Journal of enzyme inhibition and medicinal chemistry
|November 6, 2025
概括
这项研究确定了-4作为Keap1-Nrf2相互作用的强有力的循环抑制剂,为治疗炎症性疾病提供了具有最小细胞毒性的有前途的新策略.
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.
- 免疫学 免疫学 免疫学
背景情况:
- Keap1-Nrf2蛋白与蛋白相互作用是治疗炎症的关键目标.
- 目前针对这种相互作用的循环具有较低的结合亲和力.
研究的目的:
- 通过计算选和识别具有对Keap1.1高度亲和力的新型循环.
- 评估已识别的的抗炎潜力和作用机制.
主要方法:
- 计算选包括Keap1-pharmacophore建模,毒性选和分子对接.
- 在体外实验:亲和度测试,分子动力学模拟,MTT测试和LPS诱导的RAW264.7细胞中的抗炎性评估.
- 在Keap1-knockout RAW264.7巨细胞中验证,以确认Keap1的依赖性.
主要成果:
- -4通过MD模拟证明了对Keap1的强烈结合亲和力 (Kd = 7.1 ± 0.2 nM) 和稳定的结合.
- 1-6在RAW264.7巨中表现出微不足道的细胞毒性.
- -4显著抑制了LPS诱导细胞中的IL-6和TNFα表达,其活性取决于Keap1.
结论:
- -4是一种有前途的循环候选人,用于开发新型抗炎疗法.
- -4的抗炎作用是通过Keap1抑制进行的.
- 这项研究强调了循环在针对疾病治疗中的蛋白质-蛋白质相互作用方面的潜力.
更多相关视频
08:31Biosensor-based High Throughput Biopanning and Bioinformatics Analysis Strategy for the Global Validation of Drug-protein Interactions
Published on: December 1, 2020
5.5K
10:21Author Spotlight: Streamlining Protein Target Prediction and Validation via Molecular Docking and CETSA
Published on: February 23, 2024
3.6K
相关概念视频
Targeted Cancer Therapies
The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
There are several types of targeted therapies against specific...
Combination Therapies and Personalized Medicine
Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
Transducer Mechanism: Enzyme-Linked Receptors
Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
Major types that are helpful drug targets include:
Pharmacogenomics: Identification of New Drug Targets
Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...
