RU486 (MIFEPRISTONE): Mechanisms of Action and Clinical Uses

Abstract

▪ Abstract RU486 (mifepristone) has proved to be a remarkably active antiprogesterone and antiglucocorticosteroid agent in human beings. The mechanism of action involves the intracellular receptors of the antagonized hormones (progesterone and glucocorticosteroids). At the molecular level, the most important features are high binding affinity to the receptor, interaction of the phenylaminodimethyl group in the 11β-position with a specific region of the receptor binding pocket, and RU486-induced transconformation differences in the ligand-binding domain. These particularities have consequences at different steps of the receptor function as compared with agonists. However, the reasoning cannot be limited to the RU486-receptor interaction, and, for instance, there is the possibility of a switch from antagonistic property to agonist activity, depending on the intervention of other signaling pathways. It would be desirable to have derivatives with only one of the two antagonistic properties (antiprogestin, ant...