Table 2 STING antagonists [93, 137, 145, 146]^a

Nitrofurans [141]

C-176, C-178. Sub-µM and low nM potent. Inhibit mouse STING. Analogs active for both mouse and human STING. Act by covalently reacting through Cys-91 of STING to block Cys-91 palmitoylation

Indole, azaindole, benzimidazole, and related compounds [141, 147,148,149,150,151,152,153]

H-151. µM, sub-µM and low nM potent. Include indole and azaindole urea, squaramide, oxalamide, amide, and other indole derivatives. Benzimidazole derivatives described in Shen, et al. [145], as a patent. Indole H-151 blocked Cys-91 palmitoylation

Amidine [154]

BB-Cl-amidine. Inhibits STING dimerization through modification of Cys-148. Known peptidylarginine deaminase (PAD) inhibitor

Tetrahydro-iso-quinolones [138]

An optimized tetrahydro-iso-quinoline carboxylic acid inhibits STING with 68 nM. Shows EC50 > 10 µM in cGAMP-induced IFNβ production in THP1 cells

Cyclic peptide [139]

Astin C, low µM potent. Binds to the C-terminal domain of STING and possibly the CDN binding pocket

Amido-benzene-sulfonamides [140]

SN-011. Sub-µM potent. Identified and developed by virtual HTS and modification of a hit amido-benzene-sulfonamide compound. Binds and inhibits through the CDN binding pocket

Alkaloid natural product [155]

Gelsevirine. High sub-µM potent. Targets CDN binding domain and inhibits cGAMP activity. Promotes K48-linked STING ubiquitination and degradation

Others [145, 146]^a

Include dimeric benzimidazoles, dimeric furan-2-ones, 6,5-heterocyclic derivatives, purines, diadenosine triphosphate, and STING degraders