Bitonti A J, Baumann R J, Bush T L, Cashman E A, Wright C L, Prakash N J
Hoechst Marion Roussel, Inc., Cincinnati, OH 45215, USA.
Anticancer Res. 1996 Sep-Oct;16(5A):2553-7.
MDL 103,323, an enclomiphene analog, was tested for binding to the estrogen receptor, inhibition of human tumor xenografts and prevention of carcinogen-induced mammary tumors. MDL 103,323 had 5-6 fold greater affinity for the human estrogen receptor than did either tamoxifen or enclomiphene. Consistent with enhanced binding affinity, MDL 103,323 was more potent against MCF-7 cell proliferation and MCF-7 xenografts in nude mice were inhibited almost completely by MDL 103,323 doses > or = 0.02 mg/mouse/day (ED50 ł 0.01 mg/mouse/day). N-methylnitrosourea induced rat mammary carcinomas were inhibited by > or = 50% at 0.003 mg/kg daily and by 90% at 0.1 mg/kg/day. The antitumor potency and efficacy of MDL 103,323 are striking and further evaluation of the compound for potential clinical utility is warranted.
MDL 103,323，一种恩氯米芬类似物，被测试其与雌激素受体的结合能力、对人肿瘤异种移植的抑制作用以及对致癌物诱导的乳腺肿瘤的预防作用。MDL 103,323对人雌激素受体的亲和力比他莫昔芬或恩氯米芬高5至6倍。与增强的结合亲和力一致，MDL 103,323对MCF - 7细胞增殖的抑制作用更强，在裸鼠中，剂量≥0.02mg/小鼠/天的MDL 103,323几乎完全抑制了MCF - 7异种移植瘤（ED50约为0.01mg/小鼠/天）。每天0.003mg/kg剂量时，N - 甲基亚硝基脲诱导的大鼠乳腺癌受到≥50%的抑制，每天0.1mg/kg剂量时，抑制率达90%。MDL 103,323的抗肿瘤效力和效果显著，因此有必要对该化合物的潜在临床应用进行进一步评估。
