Arabinofuranosyl-5-azacytosine: activity against human tumors in athymic mice

Arabinofuranosyl-5-azacytosine (Ara-AC), a new compound structurally related to arabinofuranosylcytosine (Ara-C) and 5-azacytidine (5-AC), has demonstrated significant therapeutic activity against a wide spectrum of murine tumors and three human tumor xenografts in the NCI tumor panel. Studies on th...

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Bibliographic Details
Published in:Cancer chemotherapy and pharmacology 1989-01, Vol.25 (2), p.117-123
Main Authors: WALLACE, R. E, LINDH, D, DURR, F. E
Format: Article
Language:English
Subjects:
Animals
Antineoplastic agents
Antineoplastic Agents - therapeutic use
Azacitidine - therapeutic use
Biological and medical sciences
Cell Transformation, Neoplastic - drug effects
Chemotherapy
Cytarabine - therapeutic use
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Female
Humans
Medical sciences
Mice
Mice, Nude
Neoplasm Transplantation
Neoplasms - drug therapy
Pharmacology. Drug treatments
Stereoisomerism
Time Factors
Transplantation, Heterologous
Tumor Cells, Cultured - drug effects
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Summary:Arabinofuranosyl-5-azacytosine (Ara-AC), a new compound structurally related to arabinofuranosylcytosine (Ara-C) and 5-azacytidine (5-AC), has demonstrated significant therapeutic activity against a wide spectrum of murine tumors and three human tumor xenografts in the NCI tumor panel. Studies on the activity of Ara-AC in these and other human tumor xenograft models were undertaken to define its potential anti-human-tumor profile more completely. Ara-AC demonstrated marked antitumor activity against human tumor xenografts, including leukemias and solid tumors that do not respond to Ara-C or 5-AC. An important finding was the demonstration that Ara-AC was as effective by the oral route as when given intraperitoneally. Furthermore, the compound demonstrated synergism when combined with cisplatin in the treatment of refractory solid tumors and also induced monocyte-type differentiation of promyelocytic leukemia (HL-60) cells in vitro. Ara-AC is a promising new compound that may have utility in the treatment of human cancer beyond that anticipated for a cytotoxic nucleoside.
ISSN:0344-5704
1432-0843
DOI:10.1007/BF00692351