|CompTox Dashboard (EPA)|
|Chemical and physical data|
|Molar mass||302.408 g/mol g·mol−1|
|3D model (JSmol)|
|(what is this?)|
2-Methoxyestradiol (2-ME2) is a natural metabolite of estradiol. As an experimental drug candidate, it is being developed under the tradename of Panzem. It prevents the formation of new blood vessels that tumors need in order to grow (angiogenesis), hence it is an angiogenesis inhibitor.
2-ME2 is derived from estradiol, although it binds poorly (2000-fold lower activational potency) to known estrogen receptors. However, 2-ME2 retains activity as a high-affinity agonist of the GPER (GPR30).
Preclinical models also suggest that 2-ME2 could also be effective against inflammatory diseases such as rheumatoid arthritis. Several studies have been conducted showing 2-ME2 is a microtubule-inhibitor and effective against prostate cancer in rodents.
As of 2015[update], all clinical development of 2-ME2 has been suspended or discontinued. This is significantly due to the very poor oral bioavailability of the molecule and also due to its extensive metabolism. Analogues have been developed to overcome these problems, such as the bis-sulfamate derivative known as STX140, an oral anti-tumour agent  with improved potency, low metabolism and good pharmacokinetic properties.
As well as being a potent inhibitor of steroid sulfatase it exhibits anti-angiogenic activity, induction of cell cycle arrest and apoptosis in human tumour xenografts, with clinical potential for hormone–independent tumours. Some of this activity stems from tubulin binding at the colchicine site and disruption of interphase microtubules. STX140 is highly active in tumours that are resistant to chemotherapy.
In xenograft models of breast and prostate cancer complete cures were achieved after oral treatment and drug-resistant tumours also shrank in size after oral treatment. Conventional treatments for hormone-independent cancers targeting tubulin are associated with side effects, such as neurotoxicity, and can only be given infrequently and intravenously. STX140 is more effective on the same tumours, blocks metastatic spread without the peripheral neuropathy associated with current clinical anticancer drugs.
|Estrogen||ER RBA (%)||Uterine weight (%)|
|Notes: ER (rat uterine cytosol) RBA + estrogenicity (change in rat uterine wet weight) of estrogen metabolites. Sources: See template.|
- EntreMed's Product Information Site Archived May 4, 2005, at the Wayback Machine
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