Finerenone (BAY 94-8862) is a third-generation selective, orally active, nonsteroidal mineralocorticoid receptor (MR) antagonist with an IC50 of 18 nM[1]. Finerenone is more selective for MR than for glucocorticoid receptor (GR), androgen receptor (AR), and progesterone receptor (AR) (>500-fold)[2]. Finerenone is mainly used in the study of cardiorenal diseases, such as type 2 diabetes and chronic kidney disease[3].
In vitro, treatment of neonatal rat cardiomyocytes (NRCM) with finerenone (20 nM) reduced apoptosis stimulated by high glucose and high fatty acids, improved cardiomyocyte metabolism and reduced ROS generation via the PPARγ/CD36 pathway[4].
In vivo, oral treatment of chronic kidney disease model (MWF) and wild-type rats with finerenone (10mg/kg) significantly reduced albuminuria in MWF rats, increased endothelial nitric oxide utilization, and significantly improved endothelial function in MWF rats[5]. Finerenone (5mg/kg) was intraperitoneally injected into mice with induced retinopathy (OIR), which reduced retinal systolic pressure, gliosis, vascular leakage, and microglia/macrophage density[6]. Finerenone (10 mg/kg) was orally administered into mice with cardiac/renal inflammation model, which significantly improved the upregulation of infiltrating renal RORγt γδ-positive T cells induced by deoxycorticosterone acetate (DOCA) salt exposure and prevented cardiac and renal damage[7].
References:
[1] Liu L C Y, Schutte E, Gansevoort R T, et al. Finerenone: third-generation mineralocorticoid receptor antagonist for the treatment of heart failure and diabetic kidney disease[J]. Expert opinion on investigational drugs, 2015, 24(8): 1123-1135.
[2] Bădilă E. The expanding class of mineralocorticoid receptor modulators: New ligands for kidney, cardiac, vascular, systemic and behavioral selective actions[J]. Acta Endocrinologica (Bucharest), 2020, 16(4): 487.
[3] Agarwal R, Filippatos G, Pitt B, et al. Cardiovascular and kidney outcomes with finerenone in patients with type 2 diabetes and chronic kidney disease: the FIDELITY pooled analysis[J]. European heart journal, 2022, 43(6): 474-484.
[4] Jin T, Fu X, Liu M, et al. Finerenone attenuates myocardial apoptosis, metabolic disturbance and myocardial fibrosis in type 2 diabetes mellitus[J]. Diabetology & Metabolic Syndrome, 2023, 15(1): 87.
[5] González-Blázquez R, Somoza B, Gil-Ortega M, et al. Finerenone attenuates endothelial dysfunction and albuminuria in a chronic kidney disease model by a reduction in oxidative stress[J]. Frontiers in Pharmacology, 2018, 9: 1131.
[6] Jerome J R, Deliyanti D, Suphapimol V, et al. Finerenone, a non-steroidal mineralocorticoid receptor antagonist, reduces vascular injury and increases regulatory T-cells: Studies in rodents with diabetic and neovascular retinopathy[J]. International Journal of Molecular Sciences, 2023, 24(3): 2334.
[7] Luettges K, Bode M, Diemer J N, et al. Finerenone reduces renal RORγt γδ T cells and protects against cardiorenal damage[J]. American Journal of Nephrology, 2022, 53(7): 552-564.
非奈利酮（Finerenone；BAY 94-8862）是第三代选择性、具有口服活性的、非甾体类盐皮质激素受体 （MR）拮抗剂，IC50为18 nM[1]。Finerenone对MR的选择性高于糖皮质激素受体（GR）、雄激素受体（AR）和孕酮受体（AR）（>500-fold）[2]。Finerenone 主要用于心肾疾病研究，如2型糖尿病和慢性肾脏疾病[3]。
在体外，Finerenone（20nM）处理新生大鼠心肌细胞（NRCM），可降低高糖和高脂肪酸刺激的细胞凋亡，通过PPARγ/CD36通路改善心肌细胞代谢并减少ROS生成[4]。
在体内，Finerenone（10mg/kg）通过口服治疗慢性肾病模型（MWF）和野生型大鼠，显著减少MWF大鼠中白蛋白尿量，增加内皮一氧化氮的利用率从而显著改善MWF大鼠的内皮功能[5]。Finerenone（5mg/kg）通过腹腔注射治疗诱导性视网膜病变（OIR）小鼠，降低了视网膜收缩压，减少了神经胶质增生、血管渗漏和小胶质细胞/巨噬细胞密度[6]。Finerenone（10mg/kg）通过口服治疗心脏/肾脏炎症模型小鼠，显著改善了由醋酸脱氧皮质酮（DOCA）盐暴露引起的浸润肾RORγt γδ阳性T细胞上调，防止心肾损伤[7]。