Mooberry Susan L
Southwest Foundation for Biomedical Research, P.O. Box 760549, San Antonio, TX 78245-0549, USA.
Drug Resist Updat. 2003 Dec;6(6):355-61. doi: 10.1016/j.drup.2003.10.001.
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.
2-甲氧基雌二醇（2ME2）是雌激素的一种内源性代谢产物，具有抗血管生成和抗肿瘤作用。在临床前模型中，2ME2显示出有前景的活性，这使其作为一种口服活性的小分子血管生成抑制剂进入临床开发阶段。初步结果表明，2ME2耐受性良好，多项I期和II期临床试验正在多种肿瘤类型中评估2ME2。虽然在过去10年里许多研究增进了我们对2ME2如何发挥其多效性作用的理解，但其分子作用机制尚不清楚。最近的数据表明，2ME2可抑制缺氧诱导因子-1α（HIF-1α），这是一种关键的血管生成转录因子。2ME2抑制HIF-1α的能力与其微管解聚作用相关。细胞凋亡的外在和内在途径以及活性氧参与了2ME2引发的细胞凋亡；每条途径的相对贡献似乎因细胞类型而异。本综述重点关注截至2003年9月过去两年内发表的论文，这些论文为2ME2如何发挥其多样作用提供了重要的新见解。
