In vitro glucocorticoid receptor binding and transcriptional activation by topically active glucocorticoids.
Mometasone furoate (MF, CAS 83919-23-7, Sch 32088), budesonide (BUD, CAS 51372-29-3), fluticasone propionate (FP, CAS 80474-14-2), and triamcinolone acetonide (TA, CAS-76-25-5) are corticosteroids that are either currently available or under development for allergic rhinitis and asthma. The relative affinity of these drugs for the glucocorticoid receptor and their ability to stimulate glucocorticoid receptor-mediated transactivation of gene expression were analyzed. All of the test compounds had a higher affinity for the recombinant glucocorticoid receptor than the reference glucocorticoid receptor ligand, dexamethasone (DEX, CAS 50-02-2). In addition, all compounds showed greater potency than dexamethasone in stimulating transcription of a synthetic target gene regulated by a glucocorticoid response element. Of the compounds tested, mometasone furoate had the highest relative binding affinity for the glucocorticoid receptor, followed by fluticasone propionate, budesonide, and triamcinolone acetonide. Similarly, mometasone furoate was the most potent stimulator of glucocorticoid receptor-mediated transactivation of gene expression, followed by fluticasone propionate, tri-amcinolone acetonide, and budesonide. These in vitro studies provide a sensitive means to compare the potency of glucocorticoids and may reliably predict the in vivo topical potency of these drugs.
Smith
C L
CL
Department of Cell Biology, Baylor College of Medicine, Houston, Texas, USA.
Kreutner
W
W
D000818:Animals; D018926:Anti-Allergic Agents / Q000493:pharmacokinetics*; D018927:Anti-Asthmatic Agents / Q000493:pharmacokinetics*; D002460:Cell Line; D017930:Genes, Reporter; D005822:Genetic Vectors; D005938:Glucocorticoids / Q000493:pharmacokinetics*; D006801:Humans; D010957:Plasmids; D011965:Receptors, Glucocorticoid / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D020218:Response Elements; D015533:Transcriptional Activation
D018926:Anti-Allergic Agents; D018927:Anti-Asthmatic Agents; D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D011994:Recombinant Proteins