diABZI STING agonist (diABZI STING agonist-1, Compound 3, Tautomerism) is a potent non-nucleotide STING agonist and has tremendous potential to improve treatment of cancer in humans.
In human PBMCs, compound 3 induces dose-dependent activation of STING and secretion of IFNβ with an EC50app of 130 nM[1].
Compound 3 activates secretion of IFNβ, IL-6, TNF, and KC/GROα (also known as CXCL1) in wild-type but not Sting?/? mice. In BALB/c mice administrated 3 mg/kg compound 3 via intravenous injection, compound 3 exhibits systemic exposure with a half-life of 1.4 h and achieves systemic concentrations greater than the half-maximal effective concentration (EC50) for mouse STING (~200 ng/ml). In mice bearing subcutaneous CT-26 tumours, treatment with compound 3 results in significant tumour growth inhibition as measured by tumour volume AUC analysis (P<0.001), and significantly improves survival (P<0.001) with 8 out of 10 mice remaining tumour free at the end of the study on day 43[1].
[1] Ramanjulu JM, et al. Nature. 2018, 564(7736):439-443. [2] Abt ER, et al. Cell Rep. 2022 Jan 11;38(2):110236.