Esaxerenone (CS-3150)

Esaxerenone is a selective nonsteroidal mineralocorticoid receptor antagonist, which inhibits aldosterone-induced transcriptional activation of human mineralocorticoid receptor with no agonistic effect on mineralocorticoid receptor, and has no antagonistic or agonistic effect on glucocorticoid receptor, androgen receptor and progesterone receptor even at the high concentration of 5 μM.^[1]

For the transient transfection experiments, 293 A cells are inoculated on 100 mm dishes (4.5×10⁶ cells/dish) and cultured for 24 h in DMEM with 10% heat-inactivated FBS in 5% CO2 at 37 ℃. Then, the cells are co-transfected with each of expression plasmid and 3×GRE-Luc2P by lipofection using Lipofectamine 2000. After transfection, the cells are harvested and transferred into 96-well plates (1.0×10⁴ cells/well) containing a DMEM with 10% heat-inactivated charcoal-stripped FBS followed by incubation for 24 h. Serial dilutions of esaxerenone with or without 1 nM of the corresponding ligands for each receptor are added and further incubated for approximately 24 h. The luciferase activity of each well is measured in a multimode assay system.

In adrenalectomized rats, single oral administration of esaxerenone suppressed aldosterone-induced decrease in urinary Na(+)/K(+) ratio, an index of in vivo mineralocorticoid receptor activation, and this suppressive effect is more potent and longer-lasting than that of spironolactone and eplerenone.^[1]