ZSA-51

ZSA-51 is an orally bioavailable, small-molecule agonist of the Stimulator of Interferon Genes (STING) protein. Developed by researchers at the University of Michigan, it features a novel tricyclic benzo[4,5]thieno[2,3-c]pyrrole-1,3-dione scaffold. ZSA-51 exhibits potent activation of the STING pathway with an EC50 of 100 nM in THP1 cells, significantly outperforming earlier oral agonists like MSA-2. In preclinical models, the compound demonstrated favorable pharmacokinetic properties, including 49% oral bioavailability and preferential distribution to the lymph nodes and spleen. It has shown robust in vivo antitumor efficacy in colon and pancreatic cancer models by stimulating systemic immune responses within the tumor microenvironment.