Folitixorin (Synonyms: 5,10-Methylenetetrahydrofolic Acid, 5,10-methyl THF)

Folitixorin is a reduced form of folate and cofactor for thymidylate synthetase, the enzyme that catalyzes the methylation of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP).^1,2 It forms a ternary complex with thymidylate synthetase and fluorodeoxyuridylate (FdUMP), the active metabolite of 5-fluorouracil , that inhibits thymidylate synthetase activity and DNA synthesis.^3,2 Folitixorin has synergistic or additive cytotoxic effects against LS 174 or HT-29 human colon cancer cells, respectively, when used in combination with 5-fluorouracil.⁴ In vivo, folitixorin (0.6 mg/animal) increases survival and reduces tumor growth in an HT-29 mouse xenograft model when administered in combination with 5-fluorouracil.⁵

1.Zarow, C., Pellino, A.M., and Danenberg, P.V.Large-scale and small-scale methods for the preparation of 5,10-methylenetetrahydrofolatePrep. Biochem.12(5)381-393(1982) 2.Shirasaka, T., Shimamoto, Y., Ohshimo, H., et al.Metabolic basis of the synergistic antitumor activities of 5-fluorouracil and cisplatin in rodent tumor models in vivoCancer Chemother. Pharmacol.32(3)167-172(1993) 3.Patel, K., Yerram, S.R., Azad, N.A., et al.A thymidylate synthase ternary complex-specific antibody, FTS, permits functional monitoring of fluoropyrimidines dosingOncotarget3(7)678-685(2012) 4.Bjelogrli?, S.K., Srdi?, T., and Radulovi?, S.Comparison between cofactor and leucovorin activity applied in combination with 5-fluorouracil against two human colon cancer cell linesJ. BUON12(1)71-76(2007) 5.Cantwell, M.J., Spears, C.P., and Robbiins, J.M.Antitumor activity of combination 5,10-methylenetetrahydrofolate, 5-fluorouracil, and anti-vascular endothelial growth factor against human colorectal HT-29 tumors in nude miceJ. Clin. Oncol.22(14_suppl)3768(2004)