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Chemical Compound Review

leucovorin     (2R)-2-[[4-[(2-amino-5- methanoyl-4-oxo-1,6...

Synonyms: Leucal, Welcovorin, citrovorum, Novo-folacid, l-Leucovorin, ...
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Disease relevance of folinic acid


Psychiatry related information on folinic acid


High impact information on folinic acid


Chemical compound and disease context of folinic acid


Biological context of folinic acid


Anatomical context of folinic acid


Associations of folinic acid with other chemical compounds


Gene context of folinic acid

  • METHODS: Genotype analysis of the MTHFR gene was done in 236 patients who started MTX treatment with (n = 157) or without (n = 79) folic or folinic acid supplementation [35].
  • FOL1 is an essential gene and the nongrowth phenotype of the fol1 deletion leads to a recessive auxotrophy for folinic acid (5'-formyltetrahydrofolate) [25].
  • Since deletion of yeast FOL2 leads to a recessive auxotrophy for folinic acid, we used a yeast fol2Delta mutant for an in vivo functional assay of heterologous GTP cyclohydrolases I [36].
  • Folinic acid enhances TS inhibition by increasing the intracellular pool of folates that stabilize the 5FU-TS complex [37].
  • Mutant cells bearing a fol3 mutation require folinic acid for growth and have no dihydrofolate synthetase activity [38].

Analytical, diagnostic and therapeutic context of folinic acid


  1. Fluorouracil combined with the pure (6S)-stereoisomer of folinic acid in high doses for treatment of patients with advanced colorectal carcinoma: a phase I-II study. Machover, D., Grison, X., Goldschmidt, E., Zittoun, J., Lotz, J.P., Metzger, G., Richaud, J., Hannoun, L., Marquet, J., Guillot, T. J. Natl. Cancer Inst. (1992) [Pubmed]
  2. Fluorouracil and folinic acid in colon cancer. Hughes-Davies, L., Rescigno, J. Lancet (1995) [Pubmed]
  3. Leukopenia, trimethoprim-sulfamethoxazole, and folinic acid. Hollander, H. Ann. Intern. Med. (1985) [Pubmed]
  4. Toxicity of folic acid analogs in cultured human cells: a microtiter assay for the analysis of drug competition. Roos, D.S., Schimke, R.T. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  5. High-dose methotrexate with folinic acid in the treatment of advanced non-Hodgkin lymphoma including CNS involvement. Skarin, A.T., Zuckerman, K.S., Pitman, S.W., Rosenthal, D.S., Moloney, W., Frei, E., Canellos, G.P. Blood (1977) [Pubmed]
  6. Activation of excitatory amino acid receptors may mediate the folate-induced stimulation of locomotor activity after bilateral injection into the rat nucleus accumbens. Stephens, R.L., Lee, T., Boldry, R., Uretsky, N.J. J. Pharmacol. Exp. Ther. (1986) [Pubmed]
  7. The neurologic aspects of transcobalamin II deficiency. Hall, C.A. Br. J. Haematol. (1992) [Pubmed]
  8. Folinic acid reduces cleft lip [CL(P)] in A/WySn mice. Paros, A., Beck, S.L. Teratology (1999) [Pubmed]
  9. Cerebrospinal fluid concentrations of folate, biogenic amines and pterins in Rett syndrome: treatment with folinic acid. Ormazabal, A., Artuch, R., Vilaseca, M.A., Aracil, A., Pineda, M. Neuropediatrics. (2005) [Pubmed]
  10. Cerebral folate deficiency with developmental delay, autism, and response to folinic acid. Moretti, P., Sahoo, T., Hyland, K., Bottiglieri, T., Peters, S., del Gaudio, D., Roa, B., Curry, S., Zhu, H., Finnell, R.H., Neul, J.L., Ramaekers, V.T., Blau, N., Bacino, C.A., Miller, G., Scaglia, F. Neurology (2005) [Pubmed]
  11. Mice lacking the folic acid-binding protein Folbp1 are defective in early embryonic development. Piedrahita, J.A., Oetama, B., Bennett, G.D., van Waes, J., Kamen, B.A., Richardson, J., Lacey, S.W., Anderson, R.G., Finnell, R.H. Nat. Genet. (1999) [Pubmed]
  12. Linkage of markers controlling consecutive biochemical steps in CHO cells as demonstrated by chromosome transfer. Spandidos, D.A., Siminovitch, L. Cell (1977) [Pubmed]
  13. Immunosuppressive properties of methotrexate: apoptosis and clonal deletion of activated peripheral T cells. Genestier, L., Paillot, R., Fournel, S., Ferraro, C., Miossec, P., Revillard, J.P. J. Clin. Invest. (1998) [Pubmed]
  14. Randomised trial of systemic methotrexate versus laparoscopic salpingostomy in tubal pregnancy. Hajenius, P.J., Engelsbel, S., Mol, B.W., Van der Veen, F., Ankum, W.M., Bossuyt, P.M., Hemrika, D.J., Lammes, F.B. Lancet (1997) [Pubmed]
  15. Randomised multicentre trial of chronotherapy with oxaliplatin, fluorouracil, and folinic acid in metastatic colorectal cancer. International Organization for Cancer Chronotherapy. Lévi, F., Zidani, R., Misset, J.L. Lancet (1997) [Pubmed]
  16. Phase II trial of cisplatin, fluorouracil, and pure folinic acid for locally advanced head and neck cancer: a pharmacokinetic and clinical survey. Schneider, M., Etienne, M.C., Milano, G., Thyss, A., Otto, J., Dassonville, O., Mobayen, H., Saudes, L., Guillot, T., Demard, F. J. Clin. Oncol. (1995) [Pubmed]
  17. Biochemical and molecular properties of cisplatin-resistant A2780 cells grown in folinic acid. Lu, Y., Han, J., Scanlon, K.J. J. Biol. Chem. (1988) [Pubmed]
  18. Increase of survival benefit in advanced resectable colon cancer by extent of adjuvant treatment: results of a randomized trial comparing modulation of 5-FU + levamisole with folinic acid or with interferon-alpha. Link, K.H., Kornmann, M., Staib, L., Redenbacher, M., Kron, M., Beger, H.G. Ann. Surg. (2005) [Pubmed]
  19. Oral glutamine in the prevention of fluorouracil induced intestinal toxicity: a double blind, placebo controlled, randomised trial. Daniele, B., Perrone, F., Gallo, C., Pignata, S., De Martino, S., De Vivo, R., Barletta, E., Tambaro, R., Abbiati, R., D'Agostino, L. Gut (2001) [Pubmed]
  20. Spontaneous or imposed circadian changes in plasma concentrations of 5-fluorouracil coadministered with folinic acid and oxaliplatin: relationship with mucosal toxicity in patients with cancer. Metzger, G., Massari, C., Etienne, M.C., Comisso, M., Brienza, S., Touitou, Y., Milano, G., Bastian, G., Misset, J.L., Lévi, F. Clin. Pharmacol. Ther. (1994) [Pubmed]
  21. Homocysteine metabolism in children with Down syndrome: in vitro modulation. Pogribna, M., Melnyk, S., Pogribny, I., Chango, A., Yi, P., James, S.J. Am. J. Hum. Genet. (2001) [Pubmed]
  22. Pharmacokinetics of diastereoisomers of (6R,S)-folinic acid (leucovorin) in humans during constant high-dose intravenous infusion. Newman, E.M., Straw, J.A., Doroshow, J.H. Cancer Res. (1989) [Pubmed]
  23. Phase I clinical and pharmacokinetic study of leucovorin and infusional hepatic arterial fluorouracil. Kerr, D.J., Ledermann, J.A., McArdle, C.S., Buckels, J., Neoptolemos, J., Seymour, M., Doughty, J., Budden, J., Taylor, I. J. Clin. Oncol. (1995) [Pubmed]
  24. Effects of folinic acid on hepatoma cells containing methotrexate polyglutamates. Galivan, J., Nimec, Z. Cancer Res. (1983) [Pubmed]
  25. Characterization of the Saccharomyces cerevisiae Fol1 protein: starvation for C1 carrier induces pseudohyphal growth. Güldener, U., Koehler, G.J., Haussmann, C., Bacher, A., Kricke, J., Becher, D., Hegemann, J.H. Mol. Biol. Cell (2004) [Pubmed]
  26. Protection with single-dose folinic acid against bone-marrow depression by long-acting diaminopyrimidines. Douglas, I.D., Gordon, M.Y., Prentice, G.H., Hill, B.T., Price, L.A. Lancet (1977) [Pubmed]
  27. Schedule-dependent enhancement of the cytotoxicity of fluoropyrimidines to human carcinoma cells in the presence of folinic acid. Moran, R.G., Scanlon, K.L. Cancer Res. (1991) [Pubmed]
  28. Phase I trial of intraperitoneal iododeoxyuridine with and without intravenous high-dose folinic acid in the treatment of advanced malignancies primarily confined to the peritoneal cavity: flow cytometric and pharmacokinetic analysis. Morgan, R.J., Newman, E.M., Doroshow, J.H., McGonigle, K., Margolin, K., Raschko, J., Chow, W., Somlo, G., Leong, L., Tetef, M., Shibata, S., Hamasaki, V., Carroll, M., Vasilev, S., Akman, S., Coluzzi, P., Wagman, L., Longmate, J., Paz, B., Yen, Y., Klevecz, R. Cancer Res. (1998) [Pubmed]
  29. 5-Methyltetrahydrofolic acid, 5-formyltetrahydrofolic acid (folinic acid), and folic acid requirements of normal and Rous sarcoma virus-infected chicken fibroblasts. Balk, S.D., LeStourgeon, D., Mitchell, R.S. Cancer Res. (1978) [Pubmed]
  30. Progressive intracranial calcification in dihydropteridine reductase deficiency prior to folinic acid therapy. Woody, R.C., Brewster, M.A., Glasier, C. Neurology (1989) [Pubmed]
  31. Minidose warfarin prophylaxis for catheter-associated thrombosis in cancer patients: can it be safely associated with fluorouracil-based chemotherapy? Masci, G., Magagnoli, M., Zucali, P.A., Castagna, L., Carnaghi, C., Sarina, B., Pedicini, V., Fallini, M., Santoro, A. J. Clin. Oncol. (2003) [Pubmed]
  32. Phase III study of weekly high-dose infusional fluorouracil plus folinic acid with or without irinotecan in patients with metastatic colorectal cancer: European Organisation for Research and Treatment of Cancer Gastrointestinal Group Study 40986. Köhne, C.H., van Cutsem, E., Wils, J., Bokemeyer, C., El-Serafi, M., Lutz, M.P., Lorenz, M., Reichardt, P., Rückle-Lanz, H., Frickhofen, N., Fuchs, R., Mergenthaler, H.G., Langenbuch, T., Vanhoefer, U., Rougier, P., Voigtmann, R., Müller, L., Genicot, B., Anak, O., Nordlinger, B. J. Clin. Oncol. (2005) [Pubmed]
  33. Phase I trial of dipyridamole with 5-fluorouracil and folinic acid. Budd, G.T., Jayaraj, A., Grabowski, D., Adelstein, D., Bauer, L., Boyett, J., Bukowski, R., Murthy, S., Weick, J. Cancer Res. (1990) [Pubmed]
  34. Effects of folate receptor expression following stable transfection into wild type and methotrexate transport-deficient ZR-75-1 human breast cancer cells. Dixon, K.H., Mulligan, T., Chung, K.N., Elwood, P.C., Cowan, K.H. J. Biol. Chem. (1992) [Pubmed]
  35. The C677T mutation in the methylenetetrahydrofolate reductase gene: a genetic risk factor for methotrexate-related elevation of liver enzymes in rheumatoid arthritis patients. van Ede, A.E., Laan, R.F., Blom, H.J., Huizinga, T.W., Haagsma, C.J., Giesendorf, B.A., de Boo, T.M., van de Putte, L.B. Arthritis Rheum. (2001) [Pubmed]
  36. Complementation of the fol2 deletion in Saccharomyces cerevisiae by human and Escherichia coli genes encoding GTP cyclohydrolase I. Mancini, R., Saracino, F., Buscemi, G., Fischer, M., Schramek, N., Bracher, A., Bacher, A., Gütlich, M., Carbone, M.L. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  37. 5-fluorouracil: a pharmacological paradigm in the use of cytotoxics. Thomas, D.M., Zalcberg, J.R. Clin. Exp. Pharmacol. Physiol. (1998) [Pubmed]
  38. Polyglutamylation of folate coenzymes is necessary for methionine biosynthesis and maintenance of intact mitochondrial genome in Saccharomyces cerevisiae. Cherest, H., Thomas, D., Surdin-Kerjan, Y. J. Biol. Chem. (2000) [Pubmed]
  39. 18F-FDG PET is an early predictor of pathologic tumor response to preoperative radiochemotherapy in locally advanced rectal cancer. Cascini, G.L., Avallone, A., Delrio, P., Guida, C., Tatangelo, F., Marone, P., Aloj, L., De Martinis, F., Comella, P., Parisi, V., Lastoria, S. J. Nucl. Med. (2006) [Pubmed]
  40. Effective correction of hyperhomocysteinemia in hemodialysis patients by intravenous folinic acid and pyridoxine therapy. Touam, M., Zingraff, J., Jungers, P., Chadefaux-Vekemans, B., Drüeke, T., Massy, Z.A. Kidney Int. (1999) [Pubmed]
  41. HPLC of folinic acid diastereoisomers and 5-methyltetrahydrofolate in plasma. Etienne, M.C., Speziale, N., Milano, G. Clin. Chem. (1993) [Pubmed]
  42. Oxaliplatin. A review of its pharmacological properties and clinical efficacy in metastatic colorectal cancer and its potential in other malignancies. Culy, C.R., Clemett, D., Wiseman, L.R. Drugs (2000) [Pubmed]
  43. Population pharmacokinetics of high-dose methotrexate in children with acute lymphoblastic leukaemia. Aumente, D., Santos Buelga, D., Lukas, J.C., Gomez, P., Torres, A., Garc??a, M.J. Clinical pharmacokinetics (2006) [Pubmed]
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