A new micronized formulation of 2-methoxyestradiol-bis-sulfamate (STX140) is therapeutically potent against breast cancer.
Foster PA., Newman SP., Leese MP., Bernetiere S., Diolez C., Camara J., Hacher B., Baronnet MM., Ali T., Potter BV., Reed MJ., Purohit A.
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.