Antifolate C2 (AGF 154) has antitumor activity with an IC of 0.14 nM measured in a growth inhibition assay of human tumor cells.Antifolate C2 can be used for the study of cancer and autoimmune diseases.

Antifolate C2 (AGF154) was synthesized as a potential antitumor agent. AGF154 inhibited the proliferation of Chinese hamster ovary (CHO) sublines expressing folate receptors (FRs) α or β (IC50s < 1 nM) or the proton-coupled folate transporter (PCFT) (IC50 < 7 nM). AGF154 inhibited KB, IGROV1, and SKOV3 human tumor cells at subnanomolar concentrations, reflecting both FRα and PCFT uptake. AGF154 inhibited glycinamide ribonucleotide formyltransferase (GARFTase). In severe combined immunodeficient mice bearing SKOV3 tumors, AGF154 was efficacious. The selectivity of AGF154 for PCFT and for FRα and β over the ubiquitously expressed reduced folate carrier is a paradigm for selective tumor targeting.[1]