Esaxerenone

Esaxerenone (CS-3150) is a selective, reversible, non-steroidal, orally available, cell-permeable mineralocorticoid receptor (MR) antagonist, functioning as a "silent antagonist." Selectively binds the MR ligand-binding domain with high affinity (IC50 human ~3.7 nM for blocking aldosterone-induced transcription), inhibiting MR activation and downstream gene transcription, including profibrotic/pro-inflammatory markers. Esaxerenone exhibits over 1,000-fold selectivity for MR over other NR3C receptors, minimizing endocrine side effects compared to steroidal MRAs. Its core actions involve dose-dependent sodium/water reduction and increased potassium excretion, leading to lower blood pressure and albuminuria. Consequently, esaxerenone effectively treats hypertension and diabetic nephropathy, offering cardio-renal protection with an improved safety profile.