9-Deazaadenosine—A new potent antitumor agent
| Autor: | Ming Y. Chu, Mu-Ill Lim, Gerald W. Crabtree, Linda B. Zuckerman, Arthur E. Bogden, Seiji Sato, Robert S. Klein |
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| Rok vydání: | 1984 |
| Předmět: |
Antineoplastic Agents
Biochemistry Tubercidin Cell Line Mice chemistry.chemical_compound Adenosine deaminase In vivo Animals Humans RNA Neoplasm Uridine Immunosuppression Therapy Pharmacology biology DNA Neoplasm Neoplasms Experimental Transport inhibitor Molecular biology chemistry Deoxycoformycin biology.protein Female Ribonucleosides Thymidine Adenosine Deaminase Inhibitor Nucleoside |
| Zdroj: | Biochemical Pharmacology. 33:1229-1234 |
| ISSN: | 0006-2952 |
| Popis: | Deazaadenosine (9-DAA), a novel purine analog, was found to be a potent inhibitor of the growth of nine different human solid tumor cell lines in vitro and of pancreatic carcinoma (DAN) in antithymocyte serum (ATS)-immunosuppressed mice. In culture, IC50 values ranged from 1.1 to 8.5 X 10(-8)M. Ovarian carcinoma (MR) was the only cell line in which the activity of 9-DAA was potentiated (about 10-fold) by pretreatment with the adenosine deaminase inhibitor 2'-deoxycoformycin (dCF). After incubation of cultured pancreatic DAN cells with 9-DAA (10(-5)M) for 2 hr, a peak appeared in the triphosphate region of HPLC nucleotide profiles that was identified tentatively as 9-deazaATP. Under the same incubation conditions, the incorporation of [3H]uridine into RNA and of [3H]thymidine into DNA was inhibited by 34 and 80% respectively. In vivo studies using ATS-immunosuppressed mice showed that 9-DAA at 0.4 mg/kg/day for 3 consecutive days reduced pancreatic carcinoma (DAN) tumor weights to approximately 50% of untreated controls. The nucleoside transport inhibitor p-nitrobenzyl-6-thioinosine (NBMPR) was shown to selectively protect host tissues from 9-DAA toxicity and, thereby, potentiated the antitumor activity of 9-DAA in vivo at optimal dosages. |
| Databáze: | OpenAIRE |
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