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Arzneimittelforschung 2004; 54(11): 715-731
DOI: 10.1055/s-0031-1297029
Antibiotics · Antiviral Drugs · Chemotherapeutics · Cytostatics
Editio Cantor Verlag Aulendorf (Germany)

Anti-cancer Activity Profile of 3’-Azidothymidine 5’- [p-Methoxyphenyl Methoxyalaninyl Phosphate] (Compound 003), a Novel Nucleoside Analog

Fatih M. Uckun
Drug Discovery Program, Parker Hughes Institute, St. Paul, Minnesota, USA
,
Alexei O. Vassilev
Drug Discovery Program, Parker Hughes Institute, St. Paul, Minnesota, USA
,
Ilker Dibirdik
Drug Discovery Program, Parker Hughes Institute, St. Paul, Minnesota, USA
,
Xing-Ping Liu
Drug Discovery Program, Parker Hughes Institute, St. Paul, Minnesota, USA
,
Douglas Erbeck
Drug Discovery Program, Parker Hughes Institute, St. Paul, Minnesota, USA
,
Heather E. Tibbies
Drug Discovery Program, Parker Hughes Institute, St. Paul, Minnesota, USA
,
Sanjive Qazi
Drug Discovery Program, Parker Hughes Institute, St. Paul, Minnesota, USA
,
Taracad K. Venkatachalam
Drug Discovery Program, Parker Hughes Institute, St. Paul, Minnesota, USA
› Author Affiliations
Further Information

Publication History

Publication Date:
24 December 2011 (online)

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Summary

The novel cytotoxic nucleoside analog Compound 003 (3’-azldothymldlne 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.

Zusammenfassung

Wirkungssspektrum von 3’-Azidothymidin-5’- [p-methoxyphenyl-methoxyalaninyl-phosphat] (Substanz 003), einem neuen zytotoxischen Nukleosid-Analog

Das neue zytotoxische Nukleosid-Analog, Substanz 003 (3’-Azidothymidin-5’-[p-methoxyphenyl-methoxyalaninyl-phosphat], CAS 149560-32-7) verhinderte die bipolare Spindelorganisation und verursachte einen G2-Block im Zellzyklus von humanen Krebszellen. Mäuse und Ratten vertrugen die Verbindung 003 in einem Dosisbereich bis zu 2 g/kg ohne Anzeichen von Toxizität. Die Verbindung 003 verlängerte das krebsfreie Leben transgenen MMTVneu-Mäuse in einem HER2-positiven Brustkrebsmodell. Diese Ergebnisse deuten darauf hin, daß die Verbindung 003 in der Behandlung von Krebs-Patienten hilfreich sein könnte.

Key words

CAS 149560-32-7 - Compound 003 - HER2 positive breast cancer model - Nucleoside analog - Zidovudine derivative, anti-cancer activity profile, experimental breast cancer