使用共价小分子抑制剂向STING
Simone M Haag1, Muhammet F Gulen1, Luc Reymond2
1Global Health Institute, Swiss Federal Institute of Technology Lausanne (EPFL), Lausanne, Switzerland.
Nature
|July 6, 2018
概括
研究人员发现了阻断干扰素基因刺激蛋白 (STING) 的小分子, 这些STING抑制剂降低了炎症,并显示出治疗自身炎症疾病的潜力.
科学领域:
- 免疫学
- 分子生物学
- 药物发现
背景情况:
- 异常的先天免疫通路激活与各种疾病有关.
- 针对先天免疫的向疗法是有前途的,
- 干扰素基因刺激蛋白 (STING) 是细胞内DNA传感的一个关键介质.
研究的目的:
- 发现和表征新型小分子对抗剂的STING蛋白.
- 阐明STING抗剂抑制其功能的机制.
- 在自身炎症疾病模型中评估STING抑制的治疗潜力.
主要方法:
- 小分子STING抗剂的发现和表征.
- 研究STING抑制机制,包括向氨酸和阻断棕化.
- 评估STING抑制剂在人类和小鼠细胞中降低细胞因子的有效性.
- 在自发炎性疾病的小鼠模型中评估STING抗剂.
主要成果:
- 强效和选择性的小分子STING抗剂的鉴定.
- 证明这些化合物共价地向素91,抑制STING棕化.
- 证据表明,STING棕化对多重复合组和下游信号提供至关重要.
- 在体外减少STING介导的炎症性细胞因子产生.
- 在自发炎性疾病的小鼠模型中减弱病理特征.
结论:
- 它的功能是必不可少的,并且可以在药理上抑制.
- 小分子STING抗剂代表了对自身炎症疾病的有希望的治疗策略.
- 这项工作为STING抑制及其治疗应用提供了一种新机制.
相关概念视频
Covalent Bonds
163.2K
Overview
163.2K
Covalent Bonds
11.4K
Overview
When two atoms share electrons to complete their valence shells, they create a covalent bond. An atom's electronegativity—the force with which shared electrons are pulled towards an atom—determines how the electrons are shared. Molecules formed with covalent bonds can be either polar or nonpolar. Atoms with similar electronegativities form nonpolar covalent bonds; the electrons are shared equally. Atoms with different electronegativities share electrons unequally,...
When two atoms share electrons to complete their valence shells, they create a covalent bond. An atom's electronegativity—the force with which shared electrons are pulled towards an atom—determines how the electrons are shared. Molecules formed with covalent bonds can be either polar or nonpolar. Atoms with similar electronegativities form nonpolar covalent bonds; the electrons are shared equally. Atoms with different electronegativities share electrons unequally,...
11.4K
Covalent Bonding and Lewis Structures
61.5K
Compared to ionic bonds, which results from the transfer of electrons between metallic and nonmetallic atoms, covalent bonds result from the mutual attraction of atoms for a “shared” pair of electrons.
61.5K
Network Covalent Solids
16.2K
Network covalent solids contain a three-dimensional network of covalently bonded atoms as found in the crystal structures of nonmetals like diamond, graphite, silicon, and some covalent compounds, such as silicon dioxide (sand) and silicon carbide (carborundum, the abrasive on sandpaper). Many minerals have networks of covalent bonds.
To break or to melt a covalent network solid, covalent bonds must be broken. Because covalent bonds are relatively strong, covalent network solids are typically...
To break or to melt a covalent network solid, covalent bonds must be broken. Because covalent bonds are relatively strong, covalent network solids are typically...
16.2K
Covalently Linked Protein Regulators
9.6K
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
These groups modify specific amino acids in a protein....
9.6K
Covalently Linked Protein Regulators
2.0K
2.0K


