Definition

A selective small molecule inhibitor of ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), with potential immunomodulating and antineoplastic activities. Upon administration, ENPP1 inhibitor RBS2418 targets and binds to ENPP1, thereby inhibiting the activity of ENPP1. This inhibits ENPP1-mediated 2′-3′-cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) and adenosine triphosphate (ATP) hydrolysis and stabilizes extracellular endogenous cGAMP and ATP. This leads to the extracellular accumulation of cGAMP and ATP, and inhibits the production of immunosuppressive adenosine in the tumor microenvironment (TME). This allows for induction of anticancer immune responses. ENPP1, overexpressed in a number of tumor types, mediates nucleotide recycling by breaking down ATP to AMP, which is then converted to adenosine. It suppresses anti-tumor immune responses and increases metastasis.