The steroidal-based
drug 2-ethyloestradiol-3,17-O,O-bis-sulphamate (
STX243) has been developed as a potent antiangiogenic and antitumour compound. The objective of this study was to ascertain whether
STX243 is more active in vivo than the clinically relevant
drug 2-methoxyoestradiol (2-MeOE2) and the structurally similar compound 2-MeOE2-3,17-O,O-bis-sulphamate (
STX140). The tumour growth inhibition efficacy, antiangiogenic potential and pharmacokinetics of
STX243 were examined using four in vivo models. Both
STX243 and
STX140 were capable of retarding the growth of MDA-MB-231 xenograft tumours (72 and 63%, respectively), whereas no inhibition was observed for animals treated with 2-MeOE2. Further tumour inhibition studies showed that
STX243 was also active against MCF-7
paclitaxel-resistant tumours. Using a
Matrigel plug-based model, in vivo angiogenesis was restricted with
STX243 and
STX140 (50 and 72%, respectively, using
a 10 mg kg(-1) oral dose), thereby showing the antiangiogenic activity of both compounds. The pharmacokinetics of
STX243 were examined at two different doses using adult female rats. The compound was orally bioavailable (31% after a single 10 mg kg(-1) dose) and resistant to metabolism. These results show that
STX243 is a potent in vivo
drug and could be clinically effective at treating a number of oncological conditions.