Anti-cancer activity profile of 3'-azidothymidine 5'-[p-methoxyphenyl methoxyalaninyl phosphate] (Compound 003), a novel nucleoside analog.
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.
Uckun
Fatih M
FM
Drug Discovery Program, Parker Hughes Institute, St. Paul, Minnesota 55113, USA. fatih_uckun@ih.org
Vassilev
Alexei O
AO
Dibirdik
Ilker
I
Liu
Xing-Ping
XP
Erbeck
Douglas
D
Tibbles
Heather E
HE
Qazi
Sanjive
S
Venkatachalam
Taracad K
TK
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000633:toxicity; D001772:Blood Cell Count; D045744:Cell Line, Tumor; D018385:Centrosome / Q000187:drug effects / Q000648:ultrastructure; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D054306:Dideoxynucleotides; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry; D016195:G2 Phase / Q000187:drug effects; D020869:Gene Expression Profiling; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D008870:Microtubules / Q000187:drug effects / Q000648:ultrastructure; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D011917:Rats, Inbred Lew; D008941:Spindle Apparatus / Q000187:drug effects; D015215:Zidovudine / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000633:toxicity
C495110:3'-azidothymidine 5'-(p-methoxyphenyl methoxyalaninyl phosphate); D000970:Antineoplastic Agents; D054306:Dideoxynucleotides; D015215:Zidovudine; D004247:DNA