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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Mechanism of action of 2-methoxyestradiol: new developments.

2-Methoxyestradiol (2ME2) is an endogenous metabolite of estrogen that has both antiangiogenic and antitumor effects. In preclinical models, 2ME2 showed promising activity that led to its clinical development as an orally active, small-molecule inhibitor of angiogenesis. Initial results suggest that 2ME2 is well tolerated and several Phase I and II clinical trials are evaluating 2ME2 in multiple tumor types. While many studies over the past 10 years have increased our understanding of how 2ME2 exerts its pleiotropic effects, its molecular mechanisms of action are not yet clear. Recent data have shown that 2ME2 inhibits HIF-1alpha, a key angiogenic transcription factor. The ability of 2ME2 to inhibit HIF-1alpha correlates with its microtubule-depolymerizing effects. The extrinsic and intrinsic pathways of apoptosis and reactive oxygen species are involved in apoptosis initiated by 2ME2; the relative contribution of each pathway appears to vary depending on the cell type. This review focuses on papers published within the past 2 years up to September 2003 that provide significant new insights into how 2ME2 exerts its diverse effects.[1]


  1. Mechanism of action of 2-methoxyestradiol: new developments. Mooberry, S.L. Drug Resist. Updat. (2003) [Pubmed]
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