EntreMed, Inc., 9640 Medical Center Drive, Rockville, MD 20850, USA.
Bioorg Med Chem Lett. 2009 Nov 1;19(21):6241-4. doi: 10.1016/j.bmcl.2009.08.020. Epub 2009 Aug 8.
The syntheses of 21 analogs of 2-methoxyestradiol are presented, including ENMD-1198 which was selected for advancement into Phase 1 clinical trials in oncology. These analogs were evaluated for antiproliferative activity using breast tumor MDA-MB-231 cells, for antiangiogenic activity in HUVEC proliferation assays, and for estrogenic activity in MCF-7 cell proliferation. The most active analogs were evaluated for iv and oral pharmacokinetic properties via cassette dosing in rat and in mice pharmacokinetic models.
现介绍了 21 种 2-甲氧基雌二醇类似物的合成方法，其中包括进入肿瘤学 I 期临床试验的候选药物 ENMD-1198。这些类似物的抗增殖活性采用乳腺癌 MDA-MB-231 细胞进行评估，在 HUVEC 增殖测定中评估抗血管生成活性，在 MCF-7 细胞增殖中评估雌激素活性。通过在大鼠和小鼠药代动力学模型中进行盒式剂量给药，对最有效的类似物进行 iv 和口服药代动力学特性评价。
