Compound Screen Assay, Human HSD11B1
The apparent binding of compounds to Human HSD11B1 has been measured using differential scanning fluorimetry (DSF) technique. ..more
BioActive Compounds: 7
The apparent binding of compounds to Human HSD11B1 has been measured using differential scanning fluorimetry (DSF) technique.
In this approach, the unfolding of the protein is monitored via a fluorescent hydrophobicity-sensing dye: SYPRO orange (Invitrogen). The hyperbolic curve of increase in fluorescence intensity versus temperature shows the unfolding process. The point of inflexion of this trace provides the measured parameter known as Tm. A difference in Tm between a control without the compound and an experiment with the compound present is called a TmShift. Positive shifts indicate that the protein is more stable in the presence of the compound, indicating that the compound is bound. Since it is not possible to quantitatively compare TmShift values from different experiments containing different components, we mark positive shifts of more than 3 degrees celcius as having a PubChem assay score of 100, and all other shifts with a score of 0.
The metabolic activation of the glucocorticoid hormone cortisol from the precursor cortisone is exclusively carried out by the tissue-specific, NADPH-dependent oxidoreduction mediated by 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1, HSD11B1). This metabolic step constitutes a critical determinant in ligand-binding of cortisol to the glucocorticoid receptor. Due to the central role of cortisol in the metabolic syndrome (tetrad of obesity, insulin resistance, dyslipidemia and arterial hypertension) specific inhibition of 11beta-HSD1 emerges as a promising novel drug target in metabolic disease and other glucocorticoid-related syndromes.
Data Table (Concise)