| Candidate ID: | R1590 |
| Source ID: | DB16165 |
| Source Type: | approved; investigational |
| Compound Type: |
small molecule
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| Compound Name: |
Finerenone
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| Synonyms: |
Finerenone
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| Molecular Formula: |
C21H22N4O3
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| SMILES: |
CCOC1=NC=C(C)C2=C1[C@H](C1=CC=C(C=C1OC)C#N)C(C(N)=O)=C(C)N2
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| Structure: |
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| DrugBank Description: |
Finerenone, or BAY 94-8862, is a mineralocorticoid receptor antagonist indicated to reduce the risk of sustained decline in glomerular filtration rate, end stage kidney disease, cardiovascular death, heart attacks, and hospitalization due to heart failure in adults with chronic kidney disease associated with type II diabetes mellitus. Patients with kidney disease, would originally be given or to antagonize the mineraclocorticoid receptor. Spironolactone has low selectivity and affinity for the receptor; it dissociates quickly and can also have effects at the androgen, progesterone, and glucocorticoid receptors. Eplerenone is more selective and has longer lasting effects. More selective nonsteroidal mineralocorticoid antagonists such as , , and finerenone were later developed. So far, finerenone is the only nonsteroidal mineralocorticoid receptor antagonist to be FDA approved.
Finerenone was granted FDA approval on 9 July 2021.
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| CAS Number: |
1050477-31-0
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| Molecular Weight: |
378.432
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| DrugBank Indication: |
Finerenone is indicated to reduce the risk of sustained decline in glomerular filtration rate, end stage kidney disease, cardiovascular death, heart attacks, and hospitalization due to heart failure in adults with chronic kidney disease associated with type II diabetes mellitus.
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| DrugBank Pharmacology: |
Finerenone is a non-steroidal mineralocorticoid receptor antagonist indicated to reduce the risk of sustained decline in glomerular filtration rate, end stage kidney disease, cardiovascular death, heart attacks, and hospitalization due to heart failure in adults with chronic kidney disease associated with type II diabetes mellitus. It has a moderate duration of action as it is taken once daily, and a wide therapeutic window as patients were given doses from 1.25 mg to 80 mg in clinical trials. Patients should be counselled regarding the risk of hyperkalemia.
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| DrugBank MoA: |
Finerenone is a non-steroidal selective mineralocorticoid receptor (MR) antagonist with no significant affinity or activity at androgen, progesterone, estrogen, and glucocorticoid receptors. Animal studies have shown that finerenone binding to the MR reduces inflammation and fibrosis, and phase 2 clinical trials showed a reduction in albuminuria.
Aldosterone is a mineralocorticoid hormone involved in the regulation of blood pressure, sodium reabsorption, and potassium excretion. In 1943, agonism of the MR along with increased salt was shown to be associated with malignant hypertension, which could progress to inflammation and fibrosis of organs.
Binding of aldosterone, an MR agonist, to the MR causes a conformational change, which dissociates the receptor from inactivating chaperone proteins. The active MR translocates to the nucleus along with a complex of other coactivators to induce transcription of a number of genes.
Finerenone's binding to the MR prevents binding of MR coactivators, which in turn prevents pro-inflammatory and pro-fibrotic gene transcription.
Clinical trial data shows that blocking the mineralocorticoid receptor reduces mortality and morbidity in patients with chronic severe congestive heart failure with an ejection fraction ≤35%. Patients taking finerenone developed new onset atrial fibrillation or flutter (AFF) with a hazard ratio of 0.71. Finerenone lowered the risk of first onset of kidney failure, a sustained eGFR decrease of ≥40%, or death from a renal cause to a hazard ratio of 0.82. Cardiovascular outcomes including cardiovascular death, nonfatal heart attacks, nonfatal strokes, and hospitalization for heart failure in patients taking finerenone had a hazard ratio of 0.86 in patients with a history of AFF and 0.85 in patients without a history of AFF.
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| Targets: |
Mineralocorticoid receptor antagonist
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| Inclusion Criteria: |
Therapeutic strategy associated
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