2-Methoxyestradiol

2-Methoxyestradiol is a tubulin polymerization inhibitor and also decreases HIF-1 activity. 2-Methoxyestradiol exhibits the inhibitory activity of cellular proliferation in a breast carcinoma cell line MDA-MB-435 and an ovarian carcinoma cell line SK-OV-3 with IC50 of 1.38 μM and 1.79 μM, respectively. 2-Methoxyestradiol induces p53-induced apoptosis via two pathways: activation of p38 and NF-κB; and activation of JNK and AP-1 leading to Bcl-2 phosphorylation. Moreover, 2-Methoxyestradiol ameliorates TGF-β3-induced Smad2/3 phosphorylation and nuclear translocation, and inhibits TGF-β3-induced activation of the PI3K/Akt/mTOR pathway. 2-Methoxyestradiol also upregulates death receptor 5 and binds to tubulin, inhibiting its assembly. Preclinical models also suggest that 2ME2 could also be effective against inflammatory diseases such as rheumatoid arthritis. Several studies have been conducted showing 2ME2 is a microtubule-inhibitor and effective against prostate cancer in rodents.