8-aminoguanosine

8-aminoguanosine (8-AG) is a small molecule inhibitor of purine nucleoside phosphorylase (PNP). PNP is a key enzyme in purine metabolism that converts guanosine to guanine and inosine to hypoxanthine. In sickle cell disease (SCD), PNP activity is elevated, leading to the production of pro-oxidative and vasculotoxic metabolites. By inhibiting PNP, 8-aminoguanosine rebalances purine metabolism, improves red blood cell (RBC) deformability, and reduces sickling and hemolysis. Research conducted at the University of Pittsburgh has demonstrated its potential as a novel anti-sickling strategy in preclinical models of SCD.