The stimulator of interferon genes (STING) pathway is pivotal component of innate immunity, playing key role in host defense against viral and bacterial infections. However, aberrant activation of the STING pathway can trigger inflammatory diseases and thus inhibition of STING signaling pathway is regarded as promising anti-inflammation strategy. In this study, we designed and synthesized a series of dimeric 1-(1H-indol-3-yl) urea compounds, derivatized from the covalent STING inhibitor H151. The representative compound 3S-12 exhibited potent STING inhibitory activity with IC50 of 0.124 μM for m-STING and 0.533 μM for h-STING. In the cisplatin-induced acute kidney injury model, 3S-12 significantly alleviated tissue injury and inflammation.
