Pharm-X Center, School of Pharmaceutical Sciences, Shanghai Jiao Tong University, Shanghai, 200240, China; School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China; University of Chinese Academy of Sciences, Beijing, 100049, China.
Pharm-X Center, School of Pharmaceutical Sciences, Shanghai Jiao Tong University, Shanghai, 200240, China.
Eur J Med Chem. 2022 Aug 5;238:114480. doi: 10.1016/j.ejmech.2022.114480. Epub 2022 May 20.
Autoimmune diseases represent a class of over 80 illnesses with high incidence and prevalence and share a common pathogenesis of immune system disorders and self-attack. Over the past decade, extensive studies have demonstrated that imbalance of cGAS-STING mediated innate immune signaling is closely involved in autoimmune diseases. Over-activation of cGAS-STING pathway by mutations of STING or several exonucleases can cause accumulation of interferon and systemic inflammation. Therefore, suppression of the upregulated cGAS-STING pathway holds great potential in the treatment of human inflammatory and autoimmune diseases. Inhibitors targeting cGAS, STING and the downstream factors have been developed and pharmacologically evaluated recently. Herein, we summarize the recent advance on development of small molecular inhibitors targeting the key effectors in cGAS-STING axis as promising treatment for autoimmune diseases.
自身免疫性疾病是一大类发病率和患病率较高的疾病，具有共同的免疫紊乱和自身攻击的发病机制。在过去的十年中，广泛的研究表明，cGAS-STING 介导的固有免疫信号的失衡与自身免疫性疾病密切相关。STING 或几种核酸外切酶的突变导致 cGAS-STING 途径的过度激活，可引起干扰素和全身炎症的积累。因此，抑制上调的 cGAS-STING 途径在治疗人类炎症和自身免疫性疾病方面具有巨大的潜力。最近已经开发并药理学评估了针对 cGAS、STING 和下游因子的小分子抑制剂。本文总结了靶向 cGAS-STING 轴关键效应物的小分子抑制剂的最新进展，为自身免疫性疾病的治疗提供了有希望的治疗方法。
