2. Academic Validation
  3. Small molecules targeting cGAS-STING pathway for autoimmune disease

Small molecules targeting cGAS-STING pathway for autoimmune disease

  • Eur J Med Chem. 2022 Aug 5:238:114480. doi: 10.1016/j.ejmech.2022.114480.
Jiannan Zhao 1,  Ruoxuan Xiao 2,  Ruoqing Zeng 2,  Ende He 2,  Ao Zhang 3
Affiliations

Affiliations

  • 1 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.
  • 2 Pharm-X Center, School of Pharmaceutical Sciences, Shanghai Jiao Tong University, Shanghai, 200240, China.
  • 3 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. Electronic address: ao6919zhang@sjtu.edu.cn.
PMID: 35635952 DOI: 10.1016/j.ejmech.2022.114480
Abstract

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.

Keywords

Autoimmune disease; Innate immune; Pattern recognition receptor; Small molecular inhibitors; cGAS-STING pathway.

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