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.