2 - Methoxy estradiol Mechanisms.docVIP

 PAGE \* MERGEFORMAT 24 2 - Methoxy estradiol Mechanisms Abstract 2 - methoxy-estradiol, as estradiol metabolite, inhibits tumor growth and metastasis. Since the drug only to the proliferation of active cells play a role, but had no effect on resting cells and thus less adverse reactions, therefore increasing attention in recent years, cell cycle arrest and induce cell apoptosis and inhibits angiogenesis is its anti-tumor effect of principal mechanism. At present 2 - methoxy-estradiol has entered a phase Ⅱ clinical trial stage, and shows a good application prospects. Keywords: 2 - methoxy estradiol; cell cycle arrest; apoptosis; angiogenesis 2 - methoxy estradiol (2-methoxyestradiol) for the estradiol metabolites, estradiol 2 by the hydroxylation of carbon atoms first formed and then methylated. Chemical known as 17β-2-methoxy estrogen 1,3,5 (10) - triene -3,17 - diol. Because can inhibit angiogenesis, and less adverse reactions, while the widely used in cancer treatment, is currently in Phase II clinical study. Studies have shown that 2 - methoxy-estradiol on estrogen receptor affinity low, and the estrogen receptor agonists and antagonists did not affect its role, indicating that 2 - methoxy-estradiol does not seem to affect the female through the hormone receptor pathway play a role [1]. Pharmacological characteristics of a In recent years, that 2 - methoxy-estradiol with the anti-tumor effect and is well tolerated treatment. Cushman M et al [2] reported that 2 - methoxy-estradiol on 55 different cancer cell lines inhibited. In a multi-center, randomized, double-blind Phase II clinical trials [3], 33 androgen-resistant prostate cancer patients randomized to 400mg / d, 1200mg / d for 2 - methoxy estradiol and found that 400mg / d dose group 1 patients in drug day and the first 28 days of the peak plasma concentration (Cmax) were 2.2 ng / ml, 5.5ng/ml, 1200mg / d dose group were 2.6 ng / ml, 9.6ng / ml. Between