Repositioning Candidate Details
| Candidate ID: | R0199 |
| Source ID: | DB00695 |
| Source Type: | approved; vet_approved |
| Compound Type: | small molecule |
| Compound Name: | Furosemide |
| Synonyms: | |
| Molecular Formula: | C12H11ClN2O5S |
| SMILES: | NS(=O)(=O)C1=C(Cl)C=C(NCC2=CC=CO2)C(=C1)C(O)=O |
| Structure: |
|
| DrugBank Description: | Furosemide is a potent loop diuretic that acts on the kidneys to ultimately increase water loss from the body. It is an anthranilic acid derivative.[L7958] Furosemide is used for edema secondary to various clinical conditions, such as congestive heart failure exacerbation, liver failure, renal failure, and high blood pressure.[L7961] It mainly works by inhibiting electrolyte reabsorption from the kidneys and enhancing the excretion of water from the body. Furosemide has a fast onset and short duration of action and has been used safely and effectively in both pediatric and adult patients.[A182495] The use of furosemide is particularly beneficial in clinical settings that require a drug with a higher diuretic potential. In addition to oral formulations, the solution for intravenous and intramuscular administration is also available, which is typically limited to patients who are unable to take oral medication or for patients in emergency clinical situations.[L7958] |
| CAS Number: | 54-31-9 |
| Molecular Weight: | 330.744 |
| DrugBank Indication: | Furosemide is indicated for the treatment of edema associated with congestive heart failure, cirrhosis of the liver, and renal disease, including the nephrotic syndrome, in adults and pediatric patients.[L7958] Oral furosemide is indicated alone for the management of mild to moderate hypertension or severe hypertension in combination with other antihypertensive medications.[L9659] Intravenous furosemide is indicated as adjunctive therapy in acute pulmonary edema when a rapid onset of diuresis is desired.[L7958] |
| DrugBank Pharmacology: | Furosemide is used to manage hypertension and edema associated with congestive heart failure, cirrhosis, and renal disease, including the nephrotic syndrome. Furosemide is a potent loop diuretic that works to increase the excretion of Na+ and water by the kidneys by inhibiting their reabsorption from the proximal and distal tubules, as well as the loop of Henle.[L7958] It works directly acts on the cells of the nephron and indirectly modifies the content of the renal filtrate.[T28] Ultimately, furosemide increases the urine output by the kidney. Protein-bound furosemide is delivered to its site of action in the kidneys and secreted via active secretion by nonspecific organic transporters expressed at the luminal site of action.[A31831,L7958] Following oral administration, the onset of the diuretic effect is about 1 and 1.5 hours [L7958], and the peak effect is reached within the first 2 hours.[L7961] The duration of effect following oral administration if about 4-6 hours but may last up to 8 hours.[L9659] The onset of effect is within 5 minutes following intravenous administration and is somewhat delayed following intramuscular administration.[L7958] The peak effect is reached within 30 minutes, and the duration of effect is approximately 2 hours.[L7958] |
| DrugBank MoA: | Furosemide promotes diuresis by blocking tubular reabsorption of sodium and chloride in the proximal and distal tubules, as well as in the thick ascending loop of Henle. This is achieved through competitive inhibition of sodium-potassium-chloride cotransporters (NKCC2) expressed along these tubules in the nephron, preventing the transport of sodium ions from the lumenal side into the basolateral side for reabsorption. This inhibition results in increased excretion of water along with sodium, chloride, magnesium, calcium, hydrogen, and potassium ions.[L7961] As with other loop diuretics, furosemide decreases excretion of uric acid.[T28] Furosemide exerts direct vasodilatory effects, which results in its therapeutic effectiveness in the treatment of acute pulmonary edema. Vasodilation leads to reduced responsiveness to vasoconstrictors such as angiotensin II and noradrenaline, increased production of vasodilating prostaglandins, and decreased production of endogenous natriuretic hormones with vasoconstricting properties. Furosemide may also open potassium channels in resistance arteries.[T28] It is proposed that the main mechanism of action of furosemide is independent of its inhibitory effect on carbonic anhydrase and aldosterone.[L7958] |
| Targets: | Solute carrier family 12 member 1; Carbonic anhydrase 2; G-protein coupled receptor 35 |
| Inclusion Criteria: |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs |
|---|
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name | |
|---|---|---|---|---|---|---|---|
| T03 | Angiotensin-converting enzyme | ACE | INHIBITOR | Target is a single protein chain | P12821 | ACE_HUMAN | Details |
| T06 | Sulfonylurea receptor 1 | ABCC8 | Target is a single protein chain | Q09428 | ABCC8_HUMAN | Details | |
| T13 | Renin | REN | INHIBITOR | Target is a single protein chain | P00797 | REN_HUMAN | Details |
| T47 | Sialin | SLC17A5 | Target is a single protein chain | Q9NRA2 | SLC17A5_HUMAN | Details | |
| T15 | Steryl-sulfatase | STS | INHIBITOR | Hydrolase | P08842 | STS_HUMAN | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I02 | 1184 | nephrotic syndrome | "A nephrosis characterized by marked increase in glomerular protein permeability resulting in marked elevation of urine protein levels, hypoalbuminemia, hyperlipidemia, and hypercoagulability." [url:https\://en.wikipedia.org/wiki/Nephrotic_syndrome, url:https\://www.niddk.nih.gov/health-information/kidney-disease/nephrotic-syndrome-adults] | Details |