SR-8314

SR-8314 is a highly selective small molecule inhibitor of Ectonucleotide Pyrophosphatase/Phosphodiesterase 1 (ENPP1), developed by the Translational Genomics Research Institute (TGen). It is an analog of SR-8291, optimized for improved physiochemical and developability properties. ENPP1 acts as a natural antagonist to the STING (stimulator of interferon genes) pathway by hydrolyzing 2'3'-cGAMP, the endogenous ligand for STING. By inhibiting ENPP1, SR-8314 prevents cGAMP degradation, leading to STING pathway activation and the subsequent induction of type I interferons and pro-inflammatory cytokines. Preclinical studies in syngeneic murine models of melanoma and colorectal cancer have shown that SR-8314 promotes anti-tumor immunity, characterized by increased T-cell infiltration and a decrease in immunosuppressive tumor-associated macrophages.