AGF50

AGF50 is a novel 6-substituted thieno[2,3-d]pyrimidine (6TP) benzoyl antifolate designed for the targeted treatment of epithelial ovarian cancer (EOC). It features a 4-carbon bridge and exhibits high selectivity for cellular uptake via the folate receptor alpha (FRα), while sparing the ubiquitously expressed reduced folate carrier (RFC) and proton-coupled folate transporter (PCFT). Once inside the cell, AGF50 acts as a dual inhibitor of de novo purine nucleotide biosynthesis by targeting glycinamide ribonucleotide formyltransferase (GARFTase) and 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase (AICARFTase). This mechanism leads to the depletion of purine nucleotides and subsequent inhibition of tumor cell proliferation. Preclinical studies have demonstrated its potency against human tumor cell lines, including KB and IGROV1, with activity being specifically mediated by FRα uptake.

Other names

6-substituted thieno[2,3-d]pyrimidine antifolate