AGF320

AGF320 is a novel 5-substituted pyrrolo[3,2-d]pyrimidine analog designed to target mitochondrial and cytosolic one-carbon metabolism. It primarily inhibits serine hydroxymethyltransferase 2 (SHMT2) in the mitochondria, with secondary inhibitory effects on cytosolic targets such as SHMT1 and enzymes involved in de novo purine biosynthesis, including 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase (AICARFTase). AGF320 is selectively taken up by cells via the folate receptor alpha (FRα), which is frequently overexpressed in epithelial ovarian cancer (EOC). It also shows transport activity through the reduced folate carrier (RFC) and the proton-coupled folate transporter (PCFT). Developed by researchers at Wayne State University and Duquesne University, AGF320 has demonstrated potent anti-proliferative activity against various EOC cell lines, including those resistant to cisplatin.