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Chemical Compound Review:

AG-L-23129 3-amino-2-fluoro-propanoic acid

Synonyms: CTK8E9543, AKOS005255703, FT-0668601, PC3387E, AC1L21K0, ...

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Disease relevance of alpha-Fluoro-beta-alanine

Bone marrow cells had a toxicity profile similar to that of FUra (LD50 = 10 microM) but were relatively insensitive to FUH2 (LD50 greater than 250 microM), with no sensitivity to alpha-fluoro-beta-alanine [1].
Ehrlich ascites tumor cells were more sensitive to FUra [50% lethal dose (LD50) = 18 microM] than to FUH2 [LD50 = 50 microM], with no sensitivity to alpha-fluoro-beta-alanine even at 250 microM [1].
Using chemical shift-selective (19)F magnetic resonance (MR) imaging, we investigated the biomodulating action of 5-bromovinyluracil (BVU) on the degradation of the anticancer drug 5-fluorouracil (5-FU) to its major catabolite alpha-fluoro-beta-alanine (FBAL) and the tissue uptake of 5-FU in ACI rats with transplanted Morris hepatoma [2].

High impact information on alpha-Fluoro-beta-alanine

The 19F nuclear magnetic resonance spectra exhibited resonances representing 5-FUra, the catabolites alpha-fluoro-beta-ureidopropionic acid and alpha-fluoro-beta-alanine, as well as four distinct fluoronucleotide anabolites [3].
Concentrations of capecitabine and its metabolites [5'-deoxy-5-fluorocytidine (5'-DFCR), 5'-deoxy-5-fluorouridine (5'-DFUR), 5-FU, dihydro-5-fluorouracil (FUH2), and alpha-fluoro-beta-alanine (FBAL)] in plasma were determined by high-performance liquid chromatography or liquid chromatography/mass spectroscopy [4].
Kinetic modeling has been applied to the time course of the nuclear magnetic resonance signal intensities of 5-fluorouracil and the sum of its catabolites, alpha-fluoro-beta-ureido propanoic acid and alpha-fluoro-beta-alanine, as monitored in liver tumors of seven patients with cancer after brief intraarterial infusion of 5-fluorouracil [5].
PURPOSE: To assess the extra- and intracellular uptake of the anticancer drug fluorouracil and its major catabolite alpha-fluoro-beta-alanine (FBAL) at gadolinium-enhanced fluorine-19 magnetic resonance (MR) imaging [6].
Presently, we found that alpha-fluoro-beta-alanine (FBAL), the predominant catabolite of FUra that is formed rapidly via FUraH(2), also decreased the antitumor activity and potentiated the toxicity of FUra [7].

Biological context of alpha-Fluoro-beta-alanine

Assay of urinary alpha-fluoro-beta-alanine by gas chromatography-mass spectrometry for the biological monitoring of occupational exposure to 5-fluorouracil in oncology nurses and pharmacy technicians [8].
The biological monitoring measured detectable levels of alpha-fluoro-beta-alanine only in three nurses [9].

Anatomical context of alpha-Fluoro-beta-alanine

In the medium of rat hepatocytes incubated at low (0.1 microM) to high (2000 microM) FUDR, the majority of the metabolites consisted of the catabolite alpha-fluoro-beta-alanine [10].
Signals from the gallbladder showed a 2.2-2.4 ppm high-frequency shift from alpha-fluoro-beta-alanine, suggesting the presence of alpha-fluoro-beta-alanine-bile-acid conjugates [11].

Associations of alpha-Fluoro-beta-alanine with other chemical compounds

beta-alanine and alpha-fluoro-beta-alanine concentrative transport in rat hepatocytes is mediated by GABA transporter GAT-2 [12].
For exposure evaluation, we performed environmental monitoring of 5-fluorouracil, cytarabine, gemcitabine, cyclophosphamide, and ifosfamide in selected work areas of pharmacy and day hospital units and biological monitoring of urine for the 5-fluorouracile metabolite, alpha-fluoro-beta-alanine [9].

Gene context of alpha-Fluoro-beta-alanine

5-FU is also rapidly degraded to alpha-fluoro-beta-alanine after contact with dihydropyrimidine dehydrogenase (DPDase) which is mainly present in the liver [13].
The data obtained in non-tumour rats also demonstrated an extremely low metabolization of OGT 719 into FU and alpha-fluoro-beta-alanine, the well-known major metabolite of FU [14].

Analytical, diagnostic and therapeutic context of alpha-Fluoro-beta-alanine

In the blood of a patient treated with 5'dFUrd during a 6-h continuous perfusion, we observed unmetabolized 5'dFUrd, 5-fluorouracil, 5,6-dihydrofluorouracil, and another metabolite which has not previously been reported alpha-fluoro-beta-alanine [15].
The suppression of alpha-fluoro-beta-alanine (FBAL) formation from 5-fluorouracil (FU) is an important subject in relation to tumor chemotherapy [16].
METHODS: A catabolite of 5FU, alpha-fluoro-beta-alanine (FBAL), was measured in urine samples of two patients who underwent vitrectomy using 5FU in the infusion fluid [17].

References

Dihydrofluorouracil, a fluorouracil catabolite with antitumor activity in murine and human cells. Diasio, R.B., Schuetz, J.D., Wallace, H.J., Sommadossi, J.P. Cancer Res. (1985) [Pubmed]
Biochemical modulation of the catabolism and tissue uptake of the anticancer drug 5-fluorouracil by 5-bromovinyluracil: assessment with metabolic (19)F MR imaging. Brix, G., Bellemann, M.E., Haberkorn, U. Magnetic resonance in medicine : official journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine. (1999) [Pubmed]
Effect of modulators on 5-fluorouracil metabolite patterns in murine colon carcinoma determined by in vitro 19F nuclear magnetic resonance spectroscopy. Kamm, V.J., Rietjens, I.M., Vervoort, J., Heerschap, A., Rosenbusch, G., Hofs, H.P., Wagener, D.J. Cancer Res. (1994) [Pubmed]
Effect of food on the pharmacokinetics of capecitabine and its metabolites following oral administration in cancer patients. Reigner, B., Verweij, J., Dirix, L., Cassidy, J., Twelves, C., Allman, D., Weidekamm, E., Roos, B., Banken, L., Utoh, M., Osterwalder, B. Clin. Cancer Res. (1998) [Pubmed]
Kinetic modeling of in vivo--nuclear magnetic resonance spectroscopy data: 5-fluorouracil in liver and liver tumors. Port, R.E., Bachert, P., Semmler, W. Clin. Pharmacol. Ther. (1991) [Pubmed]
Intra- and extracellular fluorouracil uptake: assessment with contrast-enhanced metabolic F-19 MR imaging. Brix, G., Bellemann, M.E., Gerlach, L., Haberkorn, U. Radiology. (1998) [Pubmed]
alpha-fluoro-beta-alanine: effects on the antitumor activity and toxicity of 5-fluorouracil. Cao, S., Baccanari, D.P., Rustum, Y.M., Davis, S.T., Tansik, R.L., Porter, D.J., Spector, T. Biochem. Pharmacol. (2000) [Pubmed]
Assay of urinary alpha-fluoro-beta-alanine by gas chromatography-mass spectrometry for the biological monitoring of occupational exposure to 5-fluorouracil in oncology nurses and pharmacy technicians. Rubino, F.M., Verduci, C., Buratti, M., Fustinoni, S., Campo, L., Omodeo-Salè, E., Giglio, M., Iavicoli, S., Brambilla, G., Colombi, A. Biomed. Chromatogr. (2006) [Pubmed]
Evaluation of early DNA damage in healthcare workers handling antineoplastic drugs. Ursini, C.L., Cavallo, D., Colombi, A., Giglio, M., Marinaccio, A., Iavicoli, S. International archives of occupational and environmental health. (2006) [Pubmed]
Nonlinear elimination kinetics of 5-fluoro-2'-deoxyuridine in isolated perfused rat liver and isolated hepatocytes. Foth, H., Kunellis, E.M., Müseler, T., Kahl, G.F. J. Pharmacol. Exp. Ther. (1990) [Pubmed]
Gallbladder localization of (19)F MRS catabolite signals in patients receiving bolus and protracted venous infusional 5-fluorouracil. Dzik-Jurasz, A.S., Collins, D.J., Leach, M.O., Rowland, I.J. Magnetic resonance in medicine : official journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine. (2000) [Pubmed]
beta-alanine and alpha-fluoro-beta-alanine concentrative transport in rat hepatocytes is mediated by GABA transporter GAT-2. Liu, M., Russell, R.L., Beigelman, L., Handschumacher, R.E., Pizzorno, G. Am. J. Physiol. (1999) [Pubmed]
An early phase II study of oral S-1, a newly developed 5-fluorouracil derivative for advanced and recurrent gastrointestinal cancers. The S-1 Gastrointestinal Cancer Study Group. Sugimachi, K., Maehara, Y., Horikoshi, N., Shimada, Y., Sakata, Y., Mitachi, Y., Taguchi, T. Oncology (1999) [Pubmed]
Metabolism of a novel nucleoside analogue, OGT 719, in the isolated perfused rat liver model, in rats, in tumour models and in patients. Desmoulin, F., Gilard, V., Malet-Martino, M., Martino, R., Molina, C., Smith, P. Xenobiotica (2003) [Pubmed]
New approach to metabolism of 5'-deoxy-5-fluorouridine in humans with fluorine-19 NMR. Malet-Martino, M.C., Martino, R., Lopez, A., Béteille, J.P., Bon, M., Bernadou, J., Armand, J.P. Cancer Chemother. Pharmacol. (1984) [Pubmed]
In vivo 19F NMR comparative study of 5-fluorouracil, 1-(2-tetrahydrofuryl)-5-fluorouracil (FT) and an FT-uracil coadministration system in mouse tumors. Kanazawa, Y., Kurogi, S., Shinohara, S., Noda, Y., Masuda, K. Chem. Pharm. Bull. (1994) [Pubmed]
Systemic absorption of 5-fluorouracil during vitrectomy. Creten, O., Spileers, W., Stalmans, P. Am. J. Ophthalmol. (2006) [Pubmed]

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