NOVEL AROMATASE INHIBITORS

被引：28

作者：

BHATNAGAR, AS ^{[1
]}

HAUSLER, A ^{[1
]}

SCHIEWECK, K ^{[1
]}

BROWNE, LJ ^{[1
]}

BOWMAN, R ^{[1
]}

STEELE, RE ^{[1
]}

机构：

[1] CIBA GEIGY CORP,SUMMIT,NJ 07901

来源：

JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY | 1990年 / 37卷 / 03期

关键词：

D O I：

10.1016/0960-0760(90)90485-4

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Aminoglutethimide (AG), an inhibitor of the aromatase enzyme, inhibits the biosynthesis of estrogens and displays well-documented anti-tumor efficacy in breast-cancer. However, this efficacy is accompanied by a relative lack of specificity in inhibiting aromatase and moderate tolerability. We report on two new non-steroidal aromatase inhibitors (CGS 16949A and CGS 18320B) which are more potent, selective and efficacious in their inhibition of aromatase than AG. Both compound inhibit aromatase more potently in vitro and in vivo (over 400 and 1000 times respectively) than AG. They are both more selective in their inhibition of aromatase with CGS 18320B showing an improved selectively over CGS 16949A. When administered to adult female rats, both compounds elicit responses in serum hormones similar to those seen after ovariectomy. The duration of action of CGS 18320B, however, appears to be longer than that of CGS 16949A. CGS 18320B and CGS 16949A cause almost complete regression of DMBA-induced mammary tumors in adult female rats and almost completely suppress the appearance of new tumors. Thus CGS 16949A and CGS 18320B represent significant advances in the search for novel aromatase inhibitors which are more potent, selective and efficacious than aminoglutethimide.

引用

页码：363 / 367

页数：5

共 10 条

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[8] Bhatnagar, Schieweck, Hausler, Bowman, Steele, Effects of CGS 18320B, a nonsteroidal aromatase inhibitor, on nontumor-bearing and tumor-bearing rats, Abstracts 5th. Eur. Conf. on Clinical Oncology, (1989)
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