Glycinamide ribonucleotide formyltransferase (GART) is a folate-dependent enzyme required for de novo purine synthesis. Lometrexol is a folate analog antimetabolite with antineoplastic activity.1,2 At nanomolar conentrations, it inhibits GART preventing de novo purine synthesis, inhibiting DNA synthesis, arresting cells in the S phase of the cell cycle, and inhibiting tumor cell proliferation.3
1.Beardsley, G.P., Moroson, B.A., Taylor, E.C., et al.A new folate antimetabolite, 5,10-dideaza-5,6,7,8-tetrahydrofolate is a potent inhibitor of de novo purine synthesisJ. Biol. Chem.264(1)328-333(1989) 2.Pizzorno, G., Moroson, B.A., Cashmore, A.R., et al.(6R)-5,10-Dideaza-5,6,7,8-tetrahydrofolic acid effects on nucleotide metabolism in CCRF-CEM human T-lymphoblast leukemia cellsCancer Res.51(9)2291-2295(1991) 3.Bronder, J.L., and Moran, R.G.Antifolates targeting purine synthesis allow entry of tumor cells into S phase regardless of p53 functionCancer Res.62(18)5236-5241(2002)