Finerenone

Finerenone (INN, USAN) (developmental code name BAY-94-8862) is a nonsteroidal antimineralocorticoid that is in phase III clinical trials for the treatment of chronic heart failure as of October 2015. It has less relative affinity to other steroid hormone receptors than currently available antimineralocorticoids such as eplerenone and spironolactone, which should result in fewer adverse effects like gynaecomastia, impotence, and low libido[1][2]

Finerenone
Clinical data
Other namesBAY 94-8862
Routes of
administration		Oral
Drug classAntimineralocorticoid
Legal status
Legal status
  • Investigational
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.247.614
Chemical and physical data
FormulaC21H22N4O3
Molar mass378.42 g/mol g·mol−1
3D model (JSmol)

Pharmacology

Finerenone blocks mineralocorticoid receptors, which makes it a potassium-sparing diuretic.

This table compares inhibitory (blocking) concentrations (IC50, unit: nM) of three antimineralocorticoids. Mineralocorticoid receptor inhibition is responsible for the desired action of the drugs, whereas inhibition of the other receptors potentially leads to side effects. Lower values mean stronger inhibition.[3]

Spironolactone Eplerenone Finerenone
Mineralocorticoid receptor 24 990 18
Glucocorticoid receptor 2400 22,000 >10,000
Androgen receptor 77 21,200 >10,000
Progesterone receptor 740 31,200 >10,000

The above-listed drugs have insignificant affinity for the estrogen receptor.

Finerenone acts as an antagonist to mineralocorticoid receptors harboring the S810L mutation, unlike other traditional MR inhibitors such as spironolactone and eplerenone that incidentally act as agonists.[4]

Chemistry

Unlike currently marketed antimineralocorticoids, finerenone is not a steroid but a dihydropyridine derivative.

Research

The drug is also being investigated in early trials for the treatment of diabetic nephropathy.[5]

See also

References
  1. Ruilope LM, Tamargo J (April 2017). "Renin-angiotensin system blockade: Finerenone". Nephrologie & Therapeutique. 13 Suppl 1: S47–S53. doi:10.1016/j.nephro.2017.02.003. PMID 28577743.
  2. Pitt B, Anker SD, Böhm M, Gheorghiade M, Køber L, Krum H, et al. (February 2015). "Rationale and design of MinerAlocorticoid Receptor antagonist Tolerability Study-Heart Failure (ARTS-HF): a randomized study of finerenone vs. eplerenone in patients who have worsening chronic heart failure with diabetes and/or chronic kidney disease" (PDF). European Journal of Heart Failure. 17 (2): 224–32. doi:10.1002/ejhf.218. PMID 25678098.
  3. Schubert-Zsilavecz M, Wurglics M (Fall 2015). "Finerenone". Neue Arzneimittel.
  4. Amazit L, Le Billan F, Kolkhof P, Lamribet K, Viengchareun S, Fay MR, et al. (September 2015). "Finerenone Impedes Aldosterone-dependent Nuclear Import of the Mineralocorticoid Receptor and Prevents Genomic Recruitment of Steroid Receptor Coactivator-1". The Journal of Biological Chemistry. 290 (36): 21876–89. doi:10.1074/jbc.M115.657957. PMC 4571943. PMID 26203193.
  5. Bakris GL, Agarwal R, Chan JC, Cooper ME, Gansevoort RT, Haller H, et al. (September 2015). "Effect of Finerenone on Albuminuria in Patients With Diabetic Nephropathy: A Randomized Clinical Trial". JAMA. 314 (9): 884–94. doi:10.1001/jama.2015.10081. PMID 26325557.
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