Screening of anti-progestagens by receptor studies and bioassays.
A large number of potential anti-progestational compounds were screened for their ability to bind to the progesterone (MCF-7 cells) and glucocorticoid (IM-9 cells) receptors and for their activity in the pregnancy interruption test in rats. The anti-glucocorticoid activity was assessed by the effect of the compounds on body weight gain, adrenal weight and thymus weight in dexamethasone-treated rats. Of the compounds tested, two (Org 31167 and Org 31343) with the dimethylaminophenyl group at carbon atom 18 of 17 beta-hydroxy-17 alpha-(2-propenyl)-estra-4-en-3-one are equipotent with RU 38486 in the pregnancy interruption test. Both compounds possess lower anti-glucocorticoid activity than RU 38486. Since these compounds are far more active after oral than subcutaneous administration it is very likely that they become activated in the gastro-intestinal tract.
Kloosterboer
H J
HJ
Organon Scientific Development Group, Oss, The Netherlands.
Deckers
G H
GH
van der Heuvel
M J
MJ
Loozen
H J
HJ
D000021:Abortifacient Agents, Steroidal; D000818:Animals; D002460:Cell Line; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D011247:Pregnancy; D011372:Progestins / Q000037:antagonists & inhibitors*; D011817:Rabbits; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000187:drug effects*; D011980:Receptors, Progesterone / Q000187:drug effects*; D013329:Structure-Activity Relationship
D000021:Abortifacient Agents, Steroidal; D011372:Progestins; D011965:Receptors, Glucocorticoid; D011980:Receptors, Progesterone