环类抑制剂向STING的N终端尾部,并缓解自身炎症
Xiaoquan Wang1, Anqi Cao1, Wenlv Zheng1
1State Key Laboratory of Chemical Oncogenomics, Guangdong Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, 518055, China.
研究人员开发了针对干扰素基因 (STING) 途径的循环GMP-AMP合成酶 (cGAS) 刺激器的新型环胺抑制剂. 这些STING抑制剂通过阻断异常通路激活,显示出治疗炎症和自身免疫性疾病的潜力.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 药物发现 药物发现 药物发现
背景情况:
- 循环GMP-AMP合成酶 (cGAS) 刺激干扰素基因 (STING) 途径对于对病原体和细胞压力的天生的免疫力至关重要.
- 对cGAS-STING通路的失调与各种炎症和自身免疫性疾病有关.
研究的目的:
- 开发针对STING通路的新型环类抑制剂.
- 研究这些STING抑制剂的作用机制和治疗潜力.
主要方法:
- 通过修改STING的N终端尾部 (NTT) 来开发环抑制剂.
- 在人体和小鼠细胞系中对STING通路抑制的体外评估.
- 在炎症的小鼠模型 (Trex1-/-小鼠) 中对最佳抑制剂 (STi-2) 的体内评估.
主要成果:
- 开发的环类可以选择性地抑制STING通路的激活.
- 抑制剂直接与STING结合,防止其聚合和激活.
- 最优的抑制剂,STi-2,有效地减少了亲炎性细胞因子的产生和体内系统性炎症.
结论:
- 环类STING抑制剂代表了对cGAS-STING相关的自身炎症性疾病的有前途的治疗策略.
- 向STING提供了一种特定的方法来调节在炎症条件下的先天免疫反应.
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