AGF363

AGF363 is a novel 5-substituted pyrrolo[3,2-d]pyrimidine analog designed to target mitochondrial and cytosolic one-carbon (C1) metabolism. It primarily acts as an inhibitor of serine hydroxymethyltransferase 2 (SHMT2), an enzyme critical for mitochondrial C1 metabolism, while also exhibiting secondary inhibitory activity against cytosolic enzymes involved in de novo purine biosynthesis. The compound is engineered for selective tumor delivery via the folate receptor alpha (FRα), which is frequently overexpressed in epithelial ovarian cancer (EOC). Preclinical studies have demonstrated that AGF363 effectively perturbs glutathione pools and induces apoptosis in cisplatin-resistant EOC cell lines. It was developed through a collaborative research effort involving Wayne State University and Duquesne University.