A permanently charged tamoxifen derivative displays anticancer activity and improved tissue selectivity in rodents.
A quaternized form of tamoxifen (TAM), tamoxifen methiodide (TMI), was shown to demonstrate very low brain uptake compared to TAM and, unexpectedly, was considerably less estrogenic than TAM in the uterus. The agonist activity of TMI in the bone was similar to that of TAM. TMI manifested significant dose-dependent tumoricidal activity with a rapid onset of action against MCF-7 human breast cancer implants in nude mice and a mean reduction in tumor size of 60% over six weeks.
Biegon
A
A
Pharmos, Ltd., Kiryat Weizmann, Rehovot, Israel.
Brewster
M
M
Degani
H
H
Pop
E
E
Somjen
D
D
Kaye
A M
AM
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001923:Brain Chemistry; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D014018:Tissue Distribution; D014599:Uterus / Q000737:chemistry
D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen; C101859:tamoxifen methiodide