sting agonist 12

STING agonist 12b is an agonist of stimulator of interferon genes (STING).1It binds to STING (Kd= 26.4 μM) and induces interferon reporter gene expression in cells expressing human or mouse STING (EC50s = 7.45 and 10.23 μM, respectively). STING agonist 12b (40 μM) induces expression of TNF-a, IL-6, IP-10, and IL-1b in THP-1 cells. 1.Hou, S., Lan, X.-j., Li, W., et al.Design, synthesis and biological evaluation of acridone analogues as novel STING receptor agonistsBioorg. Chem.95103556(2020)

STING agonist 12L is a stimulator of interferon genes (STING) agonist that exhibits binding affinity for both wild-type STING and its variants R232, AQ, and Q with half-maximal inhibitory concentrations (IC50s) of 1.15 µM for wild-type, 1.06 µM for R232, 0.61 µM for AQ, and 1.12 µM for Q. It effectively induces reporter gene expression in THP-1 and RAW 264.7 cells, with half-maximal effective concentrations (EC50s) of 0.38 µM and 12.94 µM, respectively. At a concentration of 5 µM, STING agonist 12L escalates the expression of IFNB1, CXCL10, and IL6 mRNA in THP-1 cells. When administered in vivo at a dose of 10 mg/kg, it enhances plasma IFN-β levels and considerably reduces tumor volume and the number of lung metastases in a B16/F10 murine melanoma model.

STING activator Compound 53 based on an oxindole core structure demonstrated robust on-target functional activation of STING (human EC50 185 nM) in immortalised and primary cells and a cytokine induction fingerprint consistent with STING activation.