FR 901537

FR901537 is a new aromatase inhibitor produced by a bacterium Bacillus sp. No. 3072. Structural studies of FR901537 suggested that it was a novel naphthol derivative having pantetheine in its structure. FR901537 showed a potent inhibitory activity against aromatase from human placenta or rat ovary, but did not inhibit the activity of 11 beta-hydroxylase from bovine adrenal cortex. Lineweaver-Burk plot analysis revealed that FR901537 is a competitive inhibitor.

The pharmacological and antitumor effects of FR901537, a new aromatase inhibitor, isolated from Bacillus sp. No. 3072, were studied. Treatment for four consecutive days with FR901537 inhibited the androstenedione-induced increase in the uterus weight in immature rats. FR901537 had 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 was studied in ovariectomized, testosterone propionate (TP)-treated rats as a postmenopausal tumor model. Ovariectomy caused the regression of the mammary tumors and the growth of tumors was remarkably stimulated following TP treatment. Further, in the rats treated with FR901537 and TP, the TP-induced tumor growth was significantly inhibited by FR901537. These results suggest that FR901537 is a promising drug in the treatment of estrogen-dependent mammary tumors in postmenopausal women.