A novel class of antitumor prodrug, 1-(2'-oxopropyl)-5-fluorouracil (OFU001), that releases 5-fluorouracil upon hypoxic irradiation

Japanese Journal of Cancer Research

Volumn 91, Issue 4, 2000, Pages 433-438

  Shibamoto, Yuta ^a   Zhou, Ling ^b   Hatta, Hiroshi ^b   Mori, Mayuko ^b   Nishimoto, Sei ichi ^b  

^a KYOTO UNIVERSITY   (Japan)

^b KYOTO UNIVERSITY   (Japan)

Author keywords

5 Flourouracil; Hypoxia; Prodrug; Radiation; Radiation activated

Indexed keywords

1 (2' OXOPROPYL) 5 FLUOROURACIL; ANTINEOPLASTIC AGENT; FLUOROURACIL; PRODRUG; UNCLASSIFIED DRUG;

ANIMAL CELL; ARTICLE; CELL KILLING; CHEMICAL BINDING; CHEMICAL REACTION; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG ACTIVATION; DRUG ACTIVITY; DRUG CYTOTOXICITY; DRUG DECOMPOSITION; DRUG DESIGN; DRUG RELEASE; ELECTRON; HYPOXIA; IRRADIATION; MOUSE; NONHUMAN; PRIORITY JOURNAL; RADIOLYSIS; RADIOSENSITIZATION;

EID: 0034024791     PISSN: 09105050     EISSN: None     Source Type: Journal    
DOI: 10.1111/j.1349-7006.2000.tb00963.x     Document Type: Article

References (20)

1. Denmeade, S. R., Nagy, A., Gao, J., Lilja, H., Schally, A. V. and Isaacs, J. T. Enzymatic activation of a doxorubicinpeptide prodrug by phosphate-specific antigen. Cancer Res., 58, 2537-2540 (1998).
2. Bosslet, K., Straub, R., Blumrich, M., Caech, J., Gerken, M., Sperker, B., Kroemer, H. K., Gesson, J. P., Koch, M. and Monneret, C. Elucidation of the mechanism enabling tumor selective prodrug monotherapy. Cancer Res., 58, 1195-1201 (1998).
3. Brain, E. G., Yu, L. J., Gustafsson, K., Drewes, P. and Waxman, D. J. Modulation of P450-dependent ifosfamide pharmacokinetics: a better understanding of drug activation in vivo. Br. J. Cancer, 77, 1768-1776 (1998).
4. Kinsella, T. J., Kunugi, K. A., Vielhuber, K. A., Potter, D. M., Fritzsimmons, M. E. and Collins, J. M. Preclinical evaluation of 5-iodo-2-pyrimidinone-2′-deoxyribose as a prodrug for 5-iodo-2′-deoxyuridine-niediated radiosensitization in mouse and human tissues. Clin. Cancer Res., 4, 99-109 (1998).
5. Lawrence, T. S., Rehemtulla, A., Ng, E. Y., Wilson, M., Trosko, J. E. and Stetson, P. L. Preferential cytotoxicity of cells transduced with cytosine deaminase compared to bystander cells after treatment with 5-fluorocytosine. Cancer Res., 58, 2588-2593 (1998).
6. Mizuno, M., Yoshida, J., Colosi, P. and Kurtzman, G. Adeno-associated virus vector containing the herpes simplex virus thymidine kinase gene causes complete regression of intracerebrally implanted human gliomas in mice, in conjunction with ganciclovir administration. Jpn. J. Cancer Res., 89, 76-80 (1998).
7. Matsukura, N., Hoshino, A., Igarashi, T., Hasegawa, H., Okino, T., Onda, M., Iijima, O., Akiyama, K., Goto, T., Takubo, K., Suzuki, S. and Shimada, T. In situ gene transfer and suicide gene therapy of gastric cancer induced by N-ethyl-N′-nitro-N-nitrosoguanidine in dogs. Jpn. J. Cancer Res., 90, 1039-1049 (1999).
8. Nishimoto, S., Hatta, H., Ueshima, H. and Kagiya, T. 1-(5′-Fluoro-6′-hydroxy-5′,6′-dihydrouracil-5′-yl) -5-fluorourcil, a novel N(1)-C(5)-linked dimer that releases 5-fluorouracil by radiation activation under hypoxic conditions. J. Med. Chem., 35, 2711-2712 (1992).
9. Mori, M., Hatta, H. and Nishimoto, S. Synthesis and structure-activity relationship of radiation activating prodrugs that release 5-fluorouracil. Proceedings of the 41st Symposium on Radiation Chemistry, Kobe, Japan, 81-82 (1998).
10. Kim, J. C., Dong, E. S., Kim, J. A., Kim, S. H., Park, J. I. and Kim, S. H. Synthesis and antitumor evaluation of acyclic 5-substituted pyrimidine nucleoside analogues. Korean J. Med. Chem., 4, 111-118 (1994).
11. Shibamoto, Y., Nishimoto, S., Shimokawa, K., Hisanaga, Y., Zhou, L., Wang, J., Sasai, K., Takahashi, M., Abe, M. and Kagiya, T. Characteristics of fluorinated nitroazoles as hypoxic cell radiosensitizers. Int. J. Radiat. Oncol. Biol. Phys., 16, 1045-1048 (1989).
12. Nishimoto, S., Ide, H., Wada, T. and Kagiya, T. Radiation-induced hydroxylation of thymine promoted by electron-affinic compounds. Int. J. Radiat. Biol., 44, 585-600 (1983).
13. Shibamoto, Y., Nishimoto, S., Mi, F., Sasai, K., Kagiya, T. and Abe, M. Evaluation of various types of new hypoxic cell sensitizers using the EMT6 single cell-spheroid-solid tumour system. Int. J. Radiat. Biol., 52, 347-357 (1987).
14. Mori, M., Hatta, H., Teshima, S., Numao, Y., Fujita, S., Nishimoto, S. and Takeuchi, K. N(1)-C(5)-linked 5-fluorouracil dimer that releases 5-fluorouracil by one-electron reduction: radiation-and photo-activation mechanisms. Abstracts of Papers, Part 2, 1995 International Chemical Congress of Pacific Basin Society, Honolulu, Hawaii, 657 (1995).
15. Adams, G. E. and Dewey, D. L. Hydrated electrons and radiobiological sensitization. Biochem. Biophys. Res. Commun., 12, 473-477 (1963).
16. Santiago, A. N., Takeuchi, K., Ohga, Y., Nishida, M. and Rossi, R. A. The reactivity of 1-ehloro-3.3-dimethylbicyclo[2.2.2]octan-2-one in the radical mechanism of nucleophilic substitution. J. Org. Chem., 56, 1581-1584 (1991).
17. Wilson, W. R., Ferry, D. M., Tercel, M., Anderson, R. F. and Denny, W. A. Reduction of nitroarylmethyl quaternary ammonium prodrugs of mechloretharnine by radiation. Radiat. Res., 149, 237-245 (1998).
18. Peters, G. J., Lankelma, J., Kok, R. M., Noordhuis, P., van Groeningen, C. J., van der Wilt, C. L., Meyer, S. and Pinedo, H. M. Prolonged retention of high concentration of 5-fluorouracil in human and murine tumors as compared with plasma. Cancer Chemother. Pharmacol., 31, 269-276 (1993).
19. 1-(2′-tetrahydrofuryl)-5-fluorouracil. Clin. Cancer Res., 4, 2085-2088 (1998).
20. van Laar, J. A. M., Rustum, Y. M., Ackland, S. P., van Groeningen, C. J. and Peters, G. J. Comparison of 5-fluoro2′-deoxyuridine with 5-fluorouracil and their role in the treatment of colorectal cancer. Eur. J. Cancer, 34, 296-306 (1998).