[Hormones and antihormones. The steroidal model].
Antiglucocorticoids despite very limited clinical application (in contrast with other antisteroids) are extensively studied, since the glucocorticoid receptor, present in numerous target cells, constitute a very convenient experimental model. Structure activity relationships of a series of 17 beta-carboxamide derivatives of dexamethasone are described. The affinity of these compounds for the glucocorticoid receptor depends on the nature of the 17 beta-side chain substituent. An effect is observed at a rather large distance from the steroid nucleus. Maximal affinity is obtained with aromatic substituents. Antiglucocorticoid activity seems to be correlated with a high dissociation rate constant of the steroid receptor complexes and probably exclude the existence of a very active antiglucocorticoid in these series. Dexamethasone 17 beta-carboxamide derivates share with all other antiglucocorticoids tested the same ability to stabilize a high molecular form of the receptor associated to HSP90, a heat shock protein, in intact cells.
Formstecher
P A
PA
Laboratorie de Biochimie Structurale, Faculté de Médecine, Lille.
Lefebvre
P
P
Burollaud
T
T
D000818:Animals; D006727:Hormone Antagonists / Q000138:chemical synthesis*; D006728:Hormones / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D008956:Models, Chemical
D006727:Hormone Antagonists; D006728:Hormones
Hormones et antihormones le modèle stéroïdien.