Excessive activation of mineralocorticoid receptors by the steroid hormones aldosterone or cortisol can lead to the development of cardiovascular disease. Finerenone is a novel, potent, and selective nonsteroidal mineralocorticoid receptor antagonist with IC50 value of 18nM and exhibits no activity at any other steroid hormone receptor and on 65 receptors and ion channels (IC50>10μM). Finerenone showed a favorable PK profile and high oral bioavailability (94%) in rats[1]. Finerenone reduced cardiac hypertrophy, plasma prohormone of brain natriuretic peptide, and proteinuria more efficiently than eplerenone when comparing equinatriuretic doses. It improved systolic and diastolic left ventricular function and reduced plasma prohormone of brain natriuretic peptide levels at dose of 1mg/kg, daily, p.o., in rats that developed chronic heart failure after coronary artery ligation, suggesting that finerenone may offer end-organ protection with a reduced risk of electrolyte disturbances[2].
作用机制
Finerenone fills part of the MR binding pocket between Asn770 and Leu766[1].
Finerenone 细胞实验
Cell Line
Concentration
Treated Time
Description
References
NRK-49F fibroblasts
5µmol/L, 50µmol/L, 100µmol/L
24 hours
To investigate the effect of finerenone on aldosterone-induced Ccn2 expression in NRK-49F cells. Results showed finerenone dose-dependently prevented aldosterone-induced increase in Ccn2 mRNA levels.
Diabetol Metab Syndr. 2024 Nov 24;16(1):283.
Vascular smooth muscle cells (VSMCs)
5µmol/L
24 hours
To evaluate the effect of finerenone on aldosterone-induced Glp1r expression in VSMCs. Results showed finerenone blocked the downregulation of Glp1r by aldosterone.
Diabetol Metab Syndr. 2024 Nov 24;16(1):283.
Human kidney proximal tubular epithelial cells (HK-2 cells)
5 mM
24 hours
FIN reduced oxidative stress, mitochondrial fragmentation, and apoptosis while restoring mitophagy via the PI3K/Akt/eNOS signaling pathway.
Redox Biol. 2023 Dec;68:102946.
RAW 264.7 macrophages
5 mM
72 hours
To investigate the effect of finerenone on the expression of C5aR1 and Gnαi2 in macrophages under high glucose conditions. Results showed that finerenone significantly downregulated the expression of C5aR1 and Gnαi2 and reduced the secretion of inflammatory chemokines CXCL15 and CCL2.
Cells. 2025 Feb 26;14(5):337.
Finerenone 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
C57BL/6J male mice
High-fat diet-induced obesity model
Dietary administration
100 ppm (i.e. 0.1 g Fine/kg of diet)
For 12 weeks
To compare the metabolic and adipose tissue-specific effects of finerenone and spironolactone in a mouse model of high-fat diet-induced obesity. Results showed that finerenone increased recruitment of brown adipose tissue (iBAT) and improved insulin resistance, whereas spironolactone did not have these effects.
J Endocrinol Invest. 2022 Jan;45(1):215-220
C57BL/6J mice
High fat diet combined with streptozotocin-induced diabetes model
Dietary administration
100 mg/kg diet
For 2 weeks
To evaluate the effect of finerenone on the expression of Glp1r, Gipr, and Gcgr in the heart and kidneys of diabetic mice. Results showed finerenone attenuated the downregulation of Glp1r and Gcgr in the kidneys and Gipr in the heart of diabetic mice, and improved cardiac diastolic function (E/A ratio) and myocyte size.
Diabetol Metab Syndr. 2024 Nov 24;16(1):283.
C57BL/6J male mice
High-fat diet/streptozotocin-induced type 2 diabetic mouse model
Oral
3 mg/kg/d
Once daily for 12 weeks
FIN attenuated diabetic tubulopathy and improved renal function and mitochondrial function via the PI3K/Akt/eNOS signaling pathway.
Redox Biol. 2023 Dec;68:102946.
Mice
Diabetic nephropathy model
Oral
10 mg/kg/day
Once daily for 10 weeks
To evaluate the renal improvement of finerenone in diabetic nephropathy mice. Results showed that finerenone significantly reduced the urine albumin-to-creatinine ratio (uACR), improved tubulointerstitial injury, and inhibited the over-activation of the C5a-C5aR1 axis.
Cells. 2025 Feb 26;14(5):337.
Transgenic (mRen-2)27 rats
Diabetic and hypertensive model
Oral gavage
10 mg/kg/day
Once daily for 12 weeks
To evaluate the effects of finerenone on retinal vascular pathology and inflammation in diabetic and hypertensive rats. Results showed that finerenone reduced retinal vascular leakage, VEGF expression, and inflammatory responses.
Int J Mol Sci. 2023 Jan 25;24(3):2334
Mice
Ovariectomized mouse model
Mixed in food
1 mg/kg/day
Daily administration for 1 month
Finerenone improved left ventricular diastolic function, coronary endothelial function, exercise capacity, and metabolic parameters in ovariectomized mice.
ESC Heart Fail. 2021 Jun;8(3):1933-1943
Mice
Duchenne muscular dystrophy (DMD) model
Oral
Approximately 3 mg/kg/day
Once daily for 16 weeks
To evaluate the efficacy of finerenone as a monotherapy in improving cardiac and skeletal muscle function in a DMD model. Results showed significant improvements in cardiac strain rate and skeletal muscle grip strength, and reduced muscle damage.
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