NEW AROMATASE INHIBITOR, FR901537 .2. PHARMACOLOGICAL AND ANTITUMOR EFFECTS

The pharmacological and antitumor effects of FR901537, a new aromatase inhibitor, isolated from Bacillus sp. No. 3072, were studied. Treatme nt for four consecutive days with FR901537 inhibited the androstenedio ne-induced increase in the uterus weight in immature rats. FR901537 ha d no effect on the uterus, adrenal glands, ovary or pituitary weights in mature rats following 14 days of treatment. The antitumor activity of FR901537 on 7,12-dimethylbenz(a)anthracene-induced mammary tumors w as studied in ovariectomized, testosterone propionate (TP)-treated rat s as a postmenopausal tumor model. Ovariectomy caused the regression o f the mammary tumors and the growth of tumors was remarkably stimulate d following TP treatment. Further, in the rats treated with FR901537 a nd TP, the TP-induced tumor growth was significantly inhibited by FR90 1537. These results suggest that FR901537 is a promising drug in the t reatment of estrogen-dependent mammary tumors in postmenopausal women.