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 > 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.
Bitonti
A J
AJ
Hoechst Marion Roussel, Inc., Cincinnati, OH 45215, USA.
Baumann
R J
RJ
Bush
T L
TL
Cashman
E A
EA
Wright
C L
CL
Prakash
N J
NJ
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000378:metabolism / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D002996:Clomiphene / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use*; D004354:Drug Screening Assays, Antitumor; D064695:Enclomiphene; D005260:Female; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000517:prevention & control; D051379:Mice; D008819:Mice, Nude; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000378:metabolism; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D018931:Antineoplastic Agents, Hormonal; D011960:Receptors, Estrogen; D002996:Clomiphene; D064695:Enclomiphene