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


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.


CONCLUSIONS
The new micronized formulation of STX140 is orally bioavailable and efficacious at inhibiting MDA-MB-231 breast tumor growth.
Foster
Paul A
PA
Endocrinology and Metabolic Medicine and Sterix Ltd., Faculty of Medicine, Imperial College London, St. Mary's Hospital, London W2 1NY, UK. paul.foster@imperial.ac.uk
Newman
Simon P
SP
Leese
Mathew P
MP
Bernetiere
Sonia
S
Diolez
Christian
C
Camara
Jose
J
Hacher
Beatrice
B
Baronnet
Marie-Madeleine
MM
Ali
Tauhid
T
Potter
Barry V L
BV
Reed
Michael J
MJ
Purohit
Atul
A
D000284:Administration, Oral; D000818:Animals; D045744:Cell Line, Tumor; D004304:Dosage Forms; D004963:Estrenes / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D005260:Female; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D051381:Rats; D017207:Rats, Sprague-Dawley; D014783:Viscosity; D023041:Xenograft Model Antitumor Assays
C526438:2-methoxyestradiol-3,17-O,O-bis(sulfamate); D004304:Dosage Forms; D004963:Estrenes