caa a22 4500 386389527 CHVBK 20180307112109.0 cr unu---uuuuu 161130s1989 xx s 000 0 eng 10.1017/S0269727000010769 doi S0269727000010769 pii (NATIONALLICENCE)cambridge-10.1017/S0269727000010769 Inhibitors of oestrogen biosynthesis: preclinical studies with CGS 16949A, a new nonsteroidal aromatase inhibitor [Elektronische Daten] Inhibitors of the aromatase enzyme represent a class of therapeutic agents which potently inhibit oestrogen biosynthesis in vivo. This inhibition of oestrogen biosynthesis is well established as effective therapy in the treatment of oestrogen-dependent breast cancer. CGS 16949A [4-(5,6,7,8-tetrahydroimidazo-[l,5-a]pyridin-5-yl)-benzonitrile hydrochloride] is a non-steroidal imidazole derivative which is a potent competitive aromatase inhibitor in vitro. At a maximally effective concentration, it selectively inhibits aromatase and does not affect glucocorticoid production from the adrenal in vitro. In vivo in the rat, CGS 16949A effectively reduces ovarian oestrogen content and potently inhibits an aromatase-mediated androgen-induced uterine hypertrophy. Oral treatment of adult, cyclic female rats with CGS 16949A disrupts cyclicity, inhibits ovulation, reduces uterine weight and suppresses serum oestradiol, all expected sequelae of oestrogen deprivation. At maximally effective doses, there is no evidence of adrenal hypertrophy, indicating that adrenal steroidogenesis is unaffected. In the DMBA-induced mammary carcinoma model in the rat, CGS 16949A caused almost complete regression of palpable tumours and significantly suppressed the appearance of new tumours at a maximally effective oral dose. Thus, CGS 16949A is a potent and selective inhibitor of the aromatase enzyme. In the rat, it is very efficacious in inhibiting oestrogen biosynthesis and in suppressing the growth of DMBA-induced mammary tumours. Copyright © Royal Society of Edinburgh 1989 Oestrogen Deprivation - Novel Methods nationallicence Bhatnagar Ajay S. Research Department, Pharmaceuticals Division, CIBA-GEIGY Limited, 4002 Basel, Switzerland Schieweck Klaus Research Department, Pharmaceuticals Division, CIBA-GEIGY Limited, 4002 Basel, Switzerland Häusler Albert Research Department, Pharmaceuticals Division, CIBA-GEIGY Limited, 4002 Basel, Switzerland Browne Leslie J. Research Department, Pharmaceuticals Division, CIBA-GEIGY Corporation, Summit, NJ 07901, U.S.A. Steele Ronald E. Research Department, Pharmaceuticals Division, CIBA-GEIGY Corporation, Summit, NJ 07901, U.S.A. Proceedings of the Royal Society of Edinburgh. Section B. Biological Sciences Royal Society of Edinburgh Scotland Foundation 95(1989), 293-303 0269-7270 95<293 1989 95 PRB https://doi.org/10.1017/S0269727000010769 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1017/S0269727000010769 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Bhatnagar Ajay S. Research Department, Pharmaceuticals Division, CIBA-GEIGY Limited, 4002 Basel, Switzerland NATIONALLICENCE 700 1- Schieweck Klaus Research Department, Pharmaceuticals Division, CIBA-GEIGY Limited, 4002 Basel, Switzerland NATIONALLICENCE 700 1- Häusler Albert Research Department, Pharmaceuticals Division, CIBA-GEIGY Limited, 4002 Basel, Switzerland NATIONALLICENCE 700 1- Browne Leslie J. Research Department, Pharmaceuticals Division, CIBA-GEIGY Corporation, Summit, NJ 07901, U.S.A NATIONALLICENCE 700 1- Steele Ronald E. Research Department, Pharmaceuticals Division, CIBA-GEIGY Corporation, Summit, NJ 07901, U.S.A NATIONALLICENCE 773 0- Proceedings of the Royal Society of Edinburgh. Section B. Biological Sciences Royal Society of Edinburgh Scotland Foundation 95(1989), 293-303 0269-7270 95<293 1989 95 PRB CC0 http://creativecommons.org/publicdomain/zero/1.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-cambridge