ZSA-215 is an orally active STING agonist with an EC50 value of 3.3 μM. In the MC38 colon cancer model, ZSA-215 facilitates tumor regression and supports long-term survival in mice. It is utilized for colon cancer research.

ZSA-215 exhibits a low EC50 value of 3.3 μM in THP1-Blue ISG cells at concentrations of 2dr (0-1.5 μM) over 24 hours. In THP1 cells, ZSA-215 at 0.5-1.5 μM for 24 hours demonstrates optimal activity against STING R232 (EC50 = 9.0 μM) and mSTING (EC50 = 9.3 μM). The compound enhances STING signaling by promoting the phosphorylation of STING and IRF3, as well as the secretion of IFN-β: (1) ZSA-215 at 6-13 μM over 24 hours significantly boosts IFN-β levels in THP1 cells; (2) at 13-50 μM for 3 hours, it notably increases STING and IRF3 phosphorylation in THP1-Blue ISG cells.

Administered orally at a dose of 60 mg/kg every three days for either two or six treatments, ZSA-215 (2dr) significantly inhibits tumor growth and promotes long-term survival in the MC38 mouse tumor model.