2-Methoxyestradiol

2-Methoxyestradiol is an endogenous estrogen metabolite with low affinity for the estrogen receptor but which disrupts microtubule function. 2-Methoxyestradiol is formed by CYP450-mediated hydroxylation followed by catechol-O-methyltransferase (COMT) methylation of estradiol. 2-Methoxyestradiol is a derivative of an oestrogenic steroidal hormone and has demonstrated: potent inhibition of endothelial cell proliferation and migration and inhibition of bFGF and VEGF-induced corneal neovascularization in mice. In MDA-MB-231 cells, 2-Methoxyestradiol inhibits HIF mediated transcriptional activation of target genes without affecting the transcription of HIF-1α itself. 2-Methoxyestradiol has been shown to induce apoptosis through activation of the p53 pathway through either activation of p38 and NF-κB or JNK and AP-1 both leading to Bcl-2 phsophorylation. In addition the compound has also been observed to upregulate death receptor 5 and bind to tubulins.