Effects of 3-[N-(2-chlorobenzyl)amino]-6-(1H-imidazol-1-yl) pyridazine dihydrochloride on various aromatase enzyme systems and experimental breast cancer.
The effects of 3-[N-(2-chlorobenzyl)amino]-6-(1H-imidazol-1-yl)pyridazine dihydrochloride (CAS 124070-28-3, MFT-279) on various aromatase enzyme systems and experimental breast cancer were studied. MFT-279 inhibited the aromatase enzyme in vitro with an IC50 value of 2.39 nmol/l. On the other hand, MFT-279 had no effect on cytochrome P-450 dependent reactions of steroid biosynthesis. In pregnant mares' serum gonadotropin (PMSG)-treated female rats, the elevation of ovarian aromatase activity was significantly suppressed by the oral treatment with MFT-279 at 10 and 20 mg/kg. When MFT-279 (20 mg/kg) was orally given to 9,10-dimethyl-1,2-benzanthracene (DMBA)-treated female rats once a day for 28 days, regression of tumors was observed. These results suggest that MFT-279 may be useful for the endocrine therapy of hormone dependent mammary carcinoma.
Bandoh
K
K
Research Laboratories, Roussel Morishita, Co., Ltd., Shiga, Japan.
Ishizuka
Y
Y
Sato
M
M
D015127:9,10-Dimethyl-1,2-benzanthracene; D000311:Adrenal Glands / Q000378:metabolism; D000818:Animals; D001141:Aromatase / Q000378:metabolism; D047072:Aromatase Inhibitors; D002417:Cattle; D002784:Cholesterol / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D005260:Female; D006900:Hydroxylation; D007928:Lethal Dose 50; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy*; D051379:Mice; D008815:Mice, Inbred Strains; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology; D010053:Ovary / Q000187:drug effects / Q000201:enzymology; D010920:Placenta / Q000187:drug effects / Q000201:enzymology; D011247:Pregnancy; D011724:Pyridazines / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley
D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; C096050:MFT 279; D011724:Pyridazines; D015127:9,10-Dimethyl-1,2-benzanthracene; D003577:Cytochrome P-450 Enzyme System; D002784:Cholesterol; D001141:Aromatase