A new micronized formulation of 2-methoxyestradiol-bis-sulfamate (STX140) is therapeutically potent against breast cancer.

Abstract

UNLABELLED:

There is a continued need for orally bioavailable anticancer compounds that exhibit good efficacy against breast cancer. STX140, a derivative of 2-methoxyestradiol (2-MeOE2), has been shown to have excellent oral bioavailability and significantly reduces tumor growth. A new micronized formulation of STX140 has now been developed and its pharmacokinetics (PK) in rats and effect on MDA-MB-231 breast cancer growth in nude mice was investigated.

MATERIALS AND METHODS:

For the PK studies, female Wistar rats were treated orally with STX140 in two separate vehicles (10% tetrahydrofuran (THF) in propylene glycol (PG) or 0.5% methyl cellulose (MC) in saline) and plasma samples taken for high performance liquid chromatography analysis over 48 h. For the tumor efficacy studies, female nude mice were inoculated with MDA-MB-231 breast cancer cells and then treated orally with a range of doses of STX140.

RESULTS:

The PK studies demonstrated that the THF/PG vehicle resulted in a greater oral bioavailability of STX140 compared to the 0.5% MC vehicle. However, this was not translated to the tumor efficacy studies where STX140 at 20 mg/kg in either vehicle caused a significant reduction in tumor volume.

CONCLUSION:

The new micronized formulation of STX140 is orally bioavailable and efficacious at inhibiting MDA-MB-231 breast tumor growth.

• Authors: Paul A Foster, Simon P Newman, Mathew P Leese, Sonia Bernetiere, Christian Diolez, Jose Camara, Beatrice Hacher, Marie-Madeleine Baronnet, Tauhid Ali, Barry V L Potter, Michael J Reed, Atul Purohit
• Journal: Anticancer research (Anticancer Res) 2008 Mar-Apr Vol. 28 Issue 2A Pg. 577-81 ISSN: 0250-7005 [Print] Greece
• PMID: 18506995 (Publication Type: Comparative Study, Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 2-methoxyestradiol-3,17-O,O-bis(sulfamate)
• Dosage Forms
• Estrenes

Topics

• Administration, Oral
• Animals
• Cell Line, Tumor
• Dosage Forms
• Estrenes (administration & dosage, pharmacokinetics, therapeutic use)
• Female
• Male
• Mammary Neoplasms, Experimental (drug therapy, metabolism)
• Mice
• Mice, Nude
• Rats
• Rats, Sprague-Dawley
• Viscosity
• Xenograft Model Antitumor Assays