The mineralocorticoid receptor (or MR, MLR, MCR), also known as the aldosterone receptor or nuclear receptor subfamily 3, group C, member 2, (NR3C2) is a protein that in humans is encoded by the NR3C2 gene that is located on chromosome 4q31.1-31.2. MR is an intracellular steroid hormone receptor, and a member of the nuclear receptor superfamily, that mediates the physiological action of two important adrenal steroids, aldosterone and cortisol. Mineralocorticoid receptor is closely related to the glucocorticoid receptor (GR), and it can indifferently bind mineralocorticoid and glucocorticoid hormones. Activation of the mineralocorticoid receptor in the distal nephron by its ligand, aldosterone, plays an important role in sodium reabsorption and blood pressure regulation. Besides the regulation of sodium balance and the control of blood pressure, aldosterone-human mineralocorticoid receptor tandem also exerts important regulatory functions on the cardiovascular and central nervous systems.

Many tissues can expresse MR, such as the kidney, colon, heart, central nervous system, brown adipose tissue and sweat glands. In epithelial tissues, its activation leads to the expression of proteins regulating ionic and water transports (mainly the epithelial sodium channel or ENaC, Na+/K+ pump, serum and glucocorticoid induced kinase or SGK1) resulting in the reabsorption of sodium, and as a consequence an increase in extracellular volume, increase in blood pressure, and an excretion of potassium to maintain a normal salt concentration in the body.

Finerenone is an MR Antagonist for Cardiorenal Diseases Research

Finerenone (BAY 94-8862) is a third-generation, selective, and orally available nonsteroidal mineralocorticoid receptor (MR) antagonist (IC₅₀=18 nM). And it displays excellent selectivity versus glucocorticoid receptor (GR), androgen receptor (AR), and progesterone receptor (>500-fold). And Finerenone has the potential for cardiorenal diseases research, such as type 2 diabetes mellitus and chronic kidney disease. In vivo, Finerenone lowers albuminuria by >40% and significantly reduces systolic blood pressure (SBP) in Munich Wistar Frömter (MWF) rat.

In conclusion, Finerenone is a selective and orally available MR antagonist and has the potential for cardiorenal diseases research.

Reference

[1] ChemMedChem. 2012;7(8):1385-1403.

[2] Front Pharmacol. 2018;9:1131.