STINGagonist-46 is an orally active STING agonist that activates the STING signaling pathway, leading to the phosphorylation of TBK1 and IRF3, and enhances the secretion of IFN-β and IP-10. It directly binds to STING, increasing its thermal stability. In B16F10, CT26, and 4T1 mouse models, STINGagonist-46 demonstrates potent antitumor efficacy. This compound can be utilized for research in cancer immunotherapy.

STING agonist-46 (Compound 57), at concentrations of 0.37-30 μM over 24 hours, powerfully activates the ISG pathway in THP1-Dual cells with an EC50 of 2.55 μM. When used at 10-50 μM for 24 hours, it shows significant activation of human STING in THP1-Blue-ISG cells and murine STING in RAW-Lucia cells. Additionally, STING agonist-46 at 3.3-30 μM for 2 hours markedly promotes the phosphorylation of TBK1 and IRF3 in THP1-Dual cells. It also upregulates the expression of IFN-β and IP-10 in THP1-Dual cells at concentrations of 1.1-30 μM over 24 hours. Furthermore, at 3.3-30 μM over 48 hours, it activates both hSTING-R232 and hSTING-H232 subtypes in 293T-Dual reporter cells.

STING agonist-46 (Compound 57), administered at 500 μg per mouse via intratumoral injection or 100 mg/kg orally on days 1, 4, and 7, demonstrates significant antitumor activity against B16F10, CT26, and 4T1 tumors in immunocompetent mice. However, it shows no antitumor efficacy against B16F10 and CT26 tumors in STING knockout mice.