Fluticasone propionate and mometasone furoate have equivalent transcriptional potencies

Abstract

FP and MF have the same ability to trigger gene activation and also the same potency to inhibit AP-1 and NF-kappaB activities. Their strong transcriptional effects at 2x10(-10) M suggest that these compounds act not only topically but also systemically, with the risk of provoking concomitant adverse effects at high dosages.

Human Receptor Kinetics, Tissue Binding Affinity, and Stability of Mometasone Furoate

“…8 In contrast, Roumestan et al recently reported equivalent transcriptional activities of MF and FP. 11 In the present study, we determined the glucocorticoid concentrations necessary to induce a 50% upregulation of the anti-inflammatory protein CD163 on the membrane surface of human monocytes. We calculated effective concentrations of, for example, 0.144 nM for MF, 0.227 nM for FP, 2.12 nM for budesonide, and established a statistically significant exponential interrelationship between the RRA and the relative protein expression (Fig.…”

“…8 These results are in contrast to the conclusions of a recent study that demonstrated equivalent transcriptional potencies of MF and FP. 11 Glucocorticoids' relative potencies can be also precisely determined in ex vivo bioassays. The glucocorticoid-induced upregulation of the monocyte specific membrane protein CD163 correlates well with the corticosteroids' potencies.…”

Signal transducer and activator of transcription 1 decoy oligodeoxynucleotide suppression of contact hypersensitivity

“…Topical corticosteroids, which are widely used in the therapy of ACD, exert their anti-inflammatory effects mainly through inhibition of the transcription factors activator protein 1 (AP-1) and nuclear factor kB (NF-kB). 9 However, long-term treatment with these drugs might lead to skin atrophy, 10 and it was such drawbacks that spurred the search for alternative treatment modalities.…”

Induced-fit docking of mometasone furoate and further evidence for glucocorticoid receptor 17α pocket flexibility

“…A greater understanding of the GR over recent years has led to the development of compounds designed specifically to fit closely into the binding site, including incorporation of the furoate moiety, which appears to greatly enhance the molecular interactions between the corticosteroid and the receptor. Corticosteroid potency is measured via techniques such as the McKenzie assay, and MF has been consistently ranked as having one of the highest potencies using these methods [42,43]. Another commercial corticosteroid, FP, has recently been modified through substitution of a furoate ester (FF) in an effort to improve its pharmacologic profile.…”