Suramin potently inhibits cGAMP synthase, cGAS, in THP1 cells to modulate IFN-β levels | Zendy

Modi Wang | Zendy; Moloud Aflaki Sooreshjani | Zendy; Clinton G. Mikek | Zendy; Clement OpokuTemeng | Zendy; Herman O. Sintim | Zendy

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Suramin potently inhibits cGAMP synthase, cGAS, in THP1 cells to modulate IFN-β levels

Author(s) -

Modi Wang,

Moloud Aflaki Sooreshjani,

Clinton G. Mikek,

Clement OpokuTemeng,

Herman O. Sintim

Publication year - 2018

Publication title -

future medicinal chemistry

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 0.708

H-Index - 69

eISSN - 1756-8927

pISSN - 1756-8919

DOI - 10.4155/fmc-2017-0322

Subject(s) - suramin , stimulator of interferon genes , chemistry , sting , enzyme , microbiology and biotechnology , biology , biochemistry , receptor , pharmacology , innate immune system , engineering , aerospace engineering

Aim: Persistent activation of STING pathway is the basis for several autoimmune diseases. STING is activated by cGAMP, which is produced by cGAS in the presence of DNA. Results/methodology: HPLC-based medium throughput screening for inhibitors of cGAS identified suramin as a potent inhibitor. Unlike other reported cGAS inhibitors, which bind to the ATP/GTP binding site, suramin displaced the bound DNA from cGAS. Addition of suramin to THP1 cells reduced the levels of IFN-β mRNA and protein. Suramin did not inhibit lipopolysaccharide- or Pam3CSK4-induced IL-6 mRNA expression. Conclusion: Suramin inhibits STING pathway via the inhibition of cGAS enzymatic activity. Suramin or analogs thereof that displace DNA from cGAS could be used as anti-inflammatory drugs.

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