The Cyclopeptide Astin C Specifically Inhibits the Innate Immune CDN Sensor STING

Cell Rep. 2018 Dec 18;25(12):3405-3421.e7. doi: 10.1016/j.celrep.2018.11.097.


cGAS-STING signaling is essential for innate immunity. Its misregulation promotes cancer or autoimmune and autoinflammatory diseases, and it is imperative to identify effective lead compounds that specifically downregulate the pathway. We report here that astin C, a cyclopeptide isolated from the medicinal plant Aster tataricus, inhibits cGAS-STING signaling and the innate inflammatory responses triggered by cytosolic DNAs. Moreover, mice treated with astin C are more susceptible to HSV-1 infection. Consistently, astin C markedly attenuates the autoinflammatory responses in Trex1-/- BMDM cells and in Trex1-/- mouse autoimmune disease model. Mechanistically, astin C specifically blocks the recruitment of IRF3 onto the STING signalosome. Collectively, this study characterizes a STING-specific small-molecular inhibitor that may be applied for potentially manipulating the STING-mediated clinical diseases.

Keywords: HSV-1; IRF3; STING; TBK1; astin C; autoimmune diseases; cGAS; cyclopeptide; innate immunity; therapeutic target.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Infective Agents / metabolism
  • Autoimmune Diseases / drug therapy
  • Cytosol / metabolism
  • DNA / metabolism
  • Female
  • Gene Expression Regulation / drug effects
  • HEK293 Cells
  • Herpesvirus 1, Human / drug effects
  • Humans
  • Immunity, Innate / drug effects*
  • Inflammation / pathology
  • Interferon Regulatory Factor-3 / metabolism
  • Listeria monocytogenes / drug effects
  • Male
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Nucleotides / metabolism*
  • Peptides, Cyclic / chemistry
  • Peptides, Cyclic / pharmacology*
  • Peptides, Cyclic / therapeutic use
  • RAW 264.7 Cells
  • Signal Transduction


  • Anti-Infective Agents
  • Interferon Regulatory Factor-3
  • Membrane Proteins
  • Nucleotides
  • Peptides, Cyclic
  • Sting1 protein, mouse
  • astin C
  • DNA