AGF362

AGF362 is a novel 5-substituted pyrrolo[3,2-d]pyrimidine analog designed to target mitochondrial and cytosolic one-carbon (C1) metabolism. Developed by researchers at Wayne State University, Duquesne University, and Indiana University, it primarily inhibits serine hydroxymethyltransferase 2 (SHMT2) in the mitochondria, with secondary inhibitory effects on cytosolic targets such as SHMT1 and enzymes in the de novo purine biosynthesis pathway, including AICA ribonucleotide formyltransferase (AICARFTase). AGF362 is engineered for tumor-selective delivery via the folate receptor alpha (FRα), which is highly overexpressed in epithelial ovarian cancer (EOC). Preclinical studies have demonstrated that AGF362 exerts potent nanomolar growth inhibition against various EOC cell lines, including those resistant to cisplatin, by depleting glycine and perturbing glutathione pools, which leads to apoptosis.