N-(dibenzo[b,d]furan-3-yl)-5-nitrofuran-2-carboxamide

C-178 is a covalent inhibitor of stimulator of interferon genes (STING). It binds to Cys91 on STING to block its palmitoylation and prevents recruitment and phosphorylation of TBK1 in HEK293T cells. C-178 (0.01-1.25 μM) selectively reduces STING-, but not RIG-I- or TBK1-, mediated IFN-β reporter activity in HEK293 cells. It also prevents increases in Ifnb1 expression in bone marrow-derived macrophages (BMDMs) induced by cyclic di-GMP , double-stranded DNA, and LPS when used at a concentration of 0.5 μM.

N-(3-Dibenzofuranyl)-5-nitro-2-furancarboxamide is synthesized from Dibenzo[b,d]furan-3-amine (D418205), which is a building block used as a reactant in the preparation of dibenzofuryl(phosphonomethyl)alanines as endothelin converting enzyme inhibitors.

C-178 targets the poorly characterized N-terminal portion of mmSTING that includes the transmembrane domains. Moreover, C-178 interferes with this process by inhibiting the palmitoylation of STING. C-178 does not appreciably affect STING responses in human cells.C-178 (0-1 μM; 1 hour) alone does not appreciably affect the gene expression profile of BMDMs. In addition, it inhibits the CMA-induced phosphorylation of TBK1.C-178 (1 μM; 1 hour) decreases cdG, dsDNA, CMA and LPS-induced Ifnb1 expression in mouse bone marrow-derived macrophages.C-178 (1 μM; 0.5-4 hours) inhibits the CMA-induced p-TBK1 and sting protein expression as a time-dependent manner in mouse embryonic fibroblasts.

[1] SIMONE M. HAAG. Targeting STING with covalent small-molecule inhibitors[J]. Nature, 2018, 559 7713: 269-273. DOI:10.1038/s41586-018-0287-8