Projects

Mineralocorticoid Receptor

Endocrine disruption: Estimation of the binding affinity of small molecules towards the Mineralocorticoid receptor.

The mineralocorticoid receptor plays an important role in the regulation of renal sodium reabsorption and blood pressure control. Several recent studies provided evidence for a key role of the activation of MR in macrophage during inflammatory processes. However, the role of the mineralocorticoid receptor in macrophage remains largely unknown. Clinical trials revealed an approximately 30% reduced rate of mortality in patients with heart failure upon treatment with the MR antagonist spironolactone or eplerenone. In these patients, aldosterone concentrations are normal or even lower than in control individuals. In some studies, it is hypothesized that the mineralocorticoid receptor might be activated by the glucocorticoid cortisol, while other studies suggest a ligand-independent receptor activation by translational modification.

Mineralocorticoid receptor with bound Erythrosine.

Our QSAR study was based on a total of 48 compounds (steroids and oxindoles). 40 molecules thereof were assigned to the training set and the remaining 8 used as test compounds. The model for the mineralocorticoid receptor converged at a cross-validated r² of 0.810 and yielded a predictive r² of 0.661 for the test set.

Comparison of experimental and predicted Ki values for the mineralocorticoid receptor
(training set = black, test set = red).

Reference: Toxicol. Lett. 2009, 189, 219–224. View abstract