Abstract
The novel cytotoxic nucleoside analog Compound 003 (3'-azidothymidine 5'-[p-methoxyphenyl methoxyalaninyl phosphate], CAS 149560-32-7) prevented bipolar mitotic spindle assembly and caused a G2 arrest in human cancer cells. Compound 003 was very well tolerated by both mice and rats without any toxicity at cumulative dose levels >2 g/kg. Notably, Compound 003 prolonged cancer-free survival in the MMTVneu transgenic mouse model of HER2 positive breast cancer. These results indicate that Compound 003 may be useful in the treatment of cancer patients.
MeSH terms
-
Animals
-
Antineoplastic Agents / pharmacology*
-
Antineoplastic Agents / toxicity
-
Blood Cell Count
-
Cell Line, Tumor
-
Centrosome / drug effects
-
Centrosome / ultrastructure
-
DNA / biosynthesis
-
DNA / genetics
-
Dideoxynucleotides
-
Dose-Response Relationship, Drug
-
Female
-
Flow Cytometry
-
G2 Phase / drug effects
-
Gene Expression Profiling
-
Humans
-
Mammary Neoplasms, Experimental / drug therapy
-
Mammary Neoplasms, Experimental / pathology
-
Mice
-
Mice, Transgenic
-
Microscopy, Confocal
-
Microtubules / drug effects
-
Microtubules / ultrastructure
-
Oligonucleotide Array Sequence Analysis
-
Rats
-
Rats, Inbred Lew
-
Spindle Apparatus / drug effects
-
Zidovudine / analogs & derivatives*
-
Zidovudine / pharmacology*
-
Zidovudine / toxicity
Substances
-
3'-azidothymidine 5'-(p-methoxyphenyl methoxyalaninyl phosphate)
-
Antineoplastic Agents
-
Dideoxynucleotides
-
Zidovudine
-
DNA