Finerenone
(Synonyms: 非奈利酮,BAY 94-8862) 目录号 : GC60842
A non-steroidal mineralocorticoid receptor antagonist
Cas No.:1050477-31-0
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Finerenone is a non-steroidal mineralocorticoid receptor antagonist (IC50 = 18 nM).1 It is selective for the mineralocorticoid receptor over glucocorticoid, progesterone, and androgen receptors (IC50s = >10,000 nM for all), as well as L-type calcium channels (IC50 = >10,000 nM). Finerenone (3 mg/kg) reduces renal vasculopathy, fibrosis, and tubular degeneration, as well as cardiac fibrosis, in a rat model of hypertension-induced end-organ damage.2 It also increases exercise capacity and prevents diastolic dysfunction in ovariectomized mice.3
1.Kolkhof, P., Jaisser, F., Kim, S.-Y., et al.Steroidal and novel non-steroidal mineralocorticoid receptor antagonists in heart failure and cardiorenal diseases: Comparison at bench and bedsideHandb. Exp. Pharmacol.243271-305(2017) 2.Kolkhof, P., Hartmann, E., Freyberger, A., et al.Effects of finerenone combined with empagliflozin in a model of hypertension-induced end-organ damageAm. J. Nephrol.52(8)642-652(2021) 3.Pieronne-Deperrois, M., Guéret, A., Djerada, Z., et al.Mineralocorticoid receptor blockade with finerenone improves heart function and exercise capacity in ovariectomized miceESC Heart Fail.8(3)1933-1943(2021)
| Cas No. | 1050477-31-0 | SDF | |
| 别名 | 非奈利酮,BAY 94-8862 | ||
| Canonical SMILES | O=C(C1=C(C)NC2=C(C(OCC)=NC=C2C)[C@@H]1C3=CC=C(C#N)C=C3OC)N | ||
| 分子式 | C21H22N4O3 | 分子量 | 378.42 |
| 溶解度 | DMSO : 100 mg/mL (DMSO moisture absorption will reduce the solubility of the compound, please use a new DMSO; Need ultrasonic) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.6426 mL | 13.2128 mL | 26.4257 mL |
| 5 mM | 0.5285 mL | 2.6426 mL | 5.2851 mL |
| 10 mM | 0.2643 mL | 1.3213 mL | 2.6426 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes
N Engl J Med 2020 Dec 3;383(23):2219-2229.PMID:33264825DOI:10.1056/NEJMoa2025845.
Background: Finerenone, a nonsteroidal, selective mineralocorticoid receptor antagonist, reduced albuminuria in short-term trials involving patients with chronic kidney disease (CKD) and type 2 diabetes. However, its long-term effects on kidney and cardiovascular outcomes are unknown. Methods: In this double-blind trial, we randomly assigned 5734 patients with CKD and type 2 diabetes in a 1:1 ratio to receive Finerenone or placebo. Eligible patients had a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of 30 to less than 300, an estimated glomerular filtration rate (eGFR) of 25 to less than 60 ml per minute per 1.73 m2 of body-surface area, and diabetic retinopathy, or they had a urinary albumin-to-creatinine ratio of 300 to 5000 and an eGFR of 25 to less than 75 ml per minute per 1.73 m2. All the patients were treated with renin-angiotensin system blockade that had been adjusted before randomization to the maximum dose on the manufacturer's label that did not cause unacceptable side effects. The primary composite outcome, assessed in a time-to-event analysis, was kidney failure, a sustained decrease of at least 40% in the eGFR from baseline, or death from renal causes. The key secondary composite outcome, also assessed in a time-to-event analysis, was death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Results: During a median follow-up of 2.6 years, a primary outcome event occurred in 504 of 2833 patients (17.8%) in the Finerenone group and 600 of 2841 patients (21.1%) in the placebo group (hazard ratio, 0.82; 95% confidence interval [CI], 0.73 to 0.93; P = 0.001). A key secondary outcome event occurred in 367 patients (13.0%) and 420 patients (14.8%) in the respective groups (hazard ratio, 0.86; 95% CI, 0.75 to 0.99; P = 0.03). Overall, the frequency of adverse events was similar in the two groups. The incidence of hyperkalemia-related discontinuation of the trial regimen was higher with Finerenone than with placebo (2.3% and 0.9%, respectively). Conclusions: In patients with CKD and type 2 diabetes, treatment with Finerenone resulted in lower risks of CKD progression and cardiovascular events than placebo. (Funded by Bayer; FIDELIO-DKD ClinicalTrials.gov number, NCT02540993.).
Cardiovascular Events with Finerenone in Kidney Disease and Type 2 Diabetes
N Engl J Med 2021 Dec 9;385(24):2252-2263.PMID:34449181DOI:10.1056/NEJMoa2110956.
Background: Finerenone, a selective nonsteroidal mineralocorticoid receptor antagonist, has favorable effects on cardiorenal outcomes in patients with predominantly stage 3 or 4 chronic kidney disease (CKD) with severely elevated albuminuria and type 2 diabetes. The use of Finerenone in patients with type 2 diabetes and a wider range of CKD is unclear. Methods: In this double-blind trial, we randomly assigned patients with CKD and type 2 diabetes to receive Finerenone or placebo. Eligible patients had a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of 30 to less than 300 and an estimated glomerular filtration rate (eGFR) of 25 to 90 ml per minute per 1.73 m2 of body-surface area (stage 2 to 4 CKD) or a urinary albumin-to-creatinine ratio of 300 to 5000 and an eGFR of at least 60 ml per minute per 1.73 m2 (stage 1 or 2 CKD). Patients were treated with renin-angiotensin system blockade that had been adjusted before randomization to the maximum dose on the manufacturer's label that did not cause unacceptable side effects. The primary outcome, assessed in a time-to-event analysis, was a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. The first secondary outcome was a composite of kidney failure, a sustained decrease from baseline of at least 40% in the eGFR, or death from renal causes. Safety was assessed as investigator-reported adverse events. Results: A total of 7437 patients underwent randomization. Among the patients included in the analysis, during a median follow-up of 3.4 years, a primary outcome event occurred in 458 of 3686 patients (12.4%) in the Finerenone group and in 519 of 3666 (14.2%) in the placebo group (hazard ratio, 0.87; 95% confidence interval [CI], 0.76 to 0.98; P = 0.03), with the benefit driven primarily by a lower incidence of hospitalization for heart failure (hazard ratio, 0.71; 95% CI, 0.56 to 0.90). The secondary composite outcome occurred in 350 patients (9.5%) in the Finerenone group and in 395 (10.8%) in the placebo group (hazard ratio, 0.87; 95% CI, 0.76 to 1.01). The overall frequency of adverse events did not differ substantially between groups. The incidence of hyperkalemia-related discontinuation of the trial regimen was higher with Finerenone (1.2%) than with placebo (0.4%). Conclusions: Among patients with type 2 diabetes and stage 2 to 4 CKD with moderately elevated albuminuria or stage 1 or 2 CKD with severely elevated albuminuria, Finerenone therapy improved cardiovascular outcomes as compared with placebo. (Funded by Bayer; FIGARO-DKD ClinicalTrials.gov number, NCT02545049.).
Finerenone and Cardiovascular Outcomes in Patients With Chronic Kidney Disease and Type 2 Diabetes
Circulation 2021 Feb 9;143(6):540-552.PMID:33198491DOI:10.1161/CIRCULATIONAHA.120.051898.
Background: The FIDELIO-DKD trial (Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease) evaluated the effect of the nonsteroidal, selective mineralocorticoid receptor antagonist Finerenone on kidney and cardiovascular outcomes in patients with chronic kidney disease and type 2 diabetes with optimized renin-angiotensin system blockade. Compared with placebo, Finerenone reduced the composite kidney and cardiovascular outcomes. We report the effect of Finerenone on individual cardiovascular outcomes and in patients with and without history of atherosclerotic cardiovascular disease (CVD). Methods: This randomized, double-blind, placebo-controlled trial included patients with type 2 diabetes and urine albumin-to-creatinine ratio 30 to 5000 mg/g and an estimated glomerular filtration rate ≥25 to <75 mL per min per 1.73 m2, treated with optimized renin-angiotensin system blockade. Patients with a history of heart failure with reduced ejection fraction were excluded. Patients were randomized 1:1 to receive Finerenone or placebo. The composite cardiovascular outcome included time to cardiovascular death, myocardial infarction, stroke, or hospitalization for heart failure. Prespecified cardiovascular analyses included analyses of the components of this composite and outcomes according to CVD history at baseline. Results: Between September 2015 and June 2018, 13 911 patients were screened and 5674 were randomized; 45.9% of patients had CVD at baseline. Over a median follow-up of 2.6 years (interquartile range, 2.0-3.4 years), Finerenone reduced the risk of the composite cardiovascular outcome compared with placebo (hazard ratio, 0.86 [95% CI, 0.75-0.99]; P=0.034), with no significant interaction between patients with and without CVD (hazard ratio, 0.85 [95% CI, 0.71-1.01] in patients with a history of CVD; hazard ratio, 0.86 [95% CI, 0.68-1.08] in patients without a history of CVD; P value for interaction, 0.85). The incidence of treatment-emergent adverse events was similar between treatment arms, with a low incidence of hyperkalemia-related permanent treatment discontinuation (2.3% with Finerenone versus 0.8% with placebo in patients with CVD and 2.2% with Finerenone versus 1.0% with placebo in patients without CVD). Conclusions: Among patients with chronic kidney disease and type 2 diabetes, Finerenone reduced incidence of the composite cardiovascular outcome, with no evidence of differences in treatment effect based on preexisting CVD status. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02540993.
Cardiovascular and kidney outcomes with Finerenone in patients with type 2 diabetes and chronic kidney disease: the FIDELITY pooled analysis
Eur Heart J 2022 Feb 10;43(6):474-484.PMID:35023547DOI:10.1093/eurheartj/ehab777.
Aims: The complementary studies FIDELIO-DKD and FIGARO-DKD in patients with type 2 diabetes and chronic kidney disease (CKD) examined cardiovascular and kidney outcomes in different, overlapping stages of CKD. The purpose of the FIDELITY analysis was to perform an individual patient-level prespecified pooled efficacy and safety analysis across a broad spectrum of CKD to provide more robust estimates of safety and efficacy of Finerenone compared with placebo. Methods and results: For this prespecified analysis, two phase III, multicentre, double-blind trials involving patients with CKD and type 2 diabetes, randomized 1:1 to Finerenone or placebo, were combined. Main time-to-event efficacy outcomes were a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or hospitalization for heart failure, and a composite of kidney failure, a sustained ≥57% decrease in estimated glomerular filtration rate from baseline over ≥4 weeks, or renal death. Among 13 026 patients with a median follow-up of 3.0 years (interquartile range 2.3-3.8 years), the composite cardiovascular outcome occurred in 825 (12.7%) patients receiving Finerenone and 939 (14.4%) receiving placebo [hazard ratio (HR), 0.86; 95% confidence interval (CI), 0.78-0.95; P = 0.0018]. The composite kidney outcome occurred in 360 (5.5%) patients receiving Finerenone and 465 (7.1%) receiving placebo (HR, 0.77; 95% CI, 0.67-0.88; P = 0.0002). Overall safety outcomes were generally similar between treatment arms. Hyperkalaemia leading to permanent treatment discontinuation occurred more frequently in patients receiving Finerenone (1.7%) than placebo (0.6%). Conclusion: Finerenone reduced the risk of clinically important cardiovascular and kidney outcomes vs. placebo across the spectrum of CKD in patients with type 2 diabetes. Key question: Does Finerenone, a novel selective, nonsteroidal mineralocorticoid receptor antagonist, added to maximum tolerated renin-angiotensin system inhibition reduce cardiovascular disease and kidney disease progression over a broad range of chronic kidney disease in patients with type 2 diabetes? Key finding: In a prespecified, pooled individual-level analysis from two randomized trials, we found reductions both in cardiovascular events and kidney failure outcomes with Finerenone. Because 40% of the patients had an estimated glomerular filtration rate of >60 mL/min/1.73m2 they were identified solely on the basis of albuminuria. Take home message: Finerenone reduces the risk of clinical cardiovascular outcomes and kidney disease progression in a broad range of patients with chronic kidney disease and type 2 diabetes. Screening for albuminuria to identify at-risk patients among patients with type 2 diabetes facilitates reduction of both cardiovascular and kidney disease burden.
Finerenone: First Approval
Drugs 2021 Oct;81(15):1787-1794.PMID:34519996DOI:10.1007/s40265-021-01599-7.
Finerenone (Kerendia®), a first-in-class, orally administered, selective, nonsteroidal mineralocorticoid receptor antagonist (MRA), is being developed by Bayer HealthCare Pharmaceuticals for the treatment of diabetic kidney disease (DKD) and heart failure (HF), including chronic HF (CHF). Finerenone has been approved in the USA to reduce the risk of sustained estimated glomerular filtration rate (eGFR) decline, end stage renal disease (ESRD), cardiovascular death, nonfatal myocardial infarction (MI), and hospitalization for HF in adults with chronic kidney disease (CKD) associated with type 2 diabetes (T2D). Finerenone is undergoing regulatory assessment in the EU and in China. A phase III trial is investigating Finerenone in patients who have HF with preserved ejection fraction. This article summarizes the milestones in the development of Finerenone leading to this first approval to reduce the risk of serious kidney and heart complications in adults with CKD and T2D.