Antitumor and chemopreventive effects of a clomiphene analog, MDL 103,323, in mammary carcinoma.

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 greater than or equal to 0.02 mg/mouse/day (ED(50) (sic) 0.01 mg/mouse/day). N-methylnitrosourea induced rat mammary carcinomas were inhibited by greater than or equal to 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.