Repositioning Candidate Details
| Candidate ID: | R0197 |
| Source ID: | DB00687 |
| Source Type: | approved; investigational |
| Compound Type: | small molecule |
| Compound Name: | Fludrocortisone |
| Synonyms: | |
| Molecular Formula: | C21H29FO5 |
| SMILES: | [H][C@@]12CC[C@](O)(C(=O)CO)[C@@]1(C)C[C@H](O)[C@@]1(F)[C@@]2([H])CCC2=CC(=O)CC[C@]12C |
| Structure: |
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| DrugBank Description: | Fludrocortisone is a synthetic mineralocorticoid used in conjunction with [hydrocortisone] to replace missing endogenous corticosteroids in patients with adrenal insufficiency.[A187169,A187187] It is functionally similar to [aldosterone], the body's primary endogenous mineralocorticoid, and is structurally analogous to [cortisol], differing only by a fluorine atom at the 9-position of the steroid structure - this fluorination is thought to be crucial to fludrocortisone's significant mineralocorticoid potency.[A5423] |
| CAS Number: | 127-31-1 |
| Molecular Weight: | 380.4504 |
| DrugBank Indication: | Fludrocortisone is indicated as partial replacement therapy for primary or secondary adrenocortical insufficiency in Addison's disease. It is also indicated for the treatment of salt-losing androgenital syndrome.[L8971] |
| DrugBank Pharmacology: | Fludrocortisone is a synthetic mineralocorticoid used to replace endogenous [aldosterone] in conditions resulting in missing or inadequate endogenous synthesis.[L8971,L8974] It acts on the kidneys to increase both sodium reabsorption and potassium excretion.[T28,A187187] As its effects are exerted at the transcriptional level, a single dose of fludrocortisone may work over the course of 1-2 days[L8974] despite a relatively short plasma half-life.[A187159,A187169,A187181] Like other systemic corticosteroids, fludrocortisone may mask signs of infection by depressing the normal immune response - infections occurring during fludrocortisone therapy should be promptly treated with appropriate antimicrobial therapy.[L8971] |
| DrugBank MoA: | The main endogenous mineralocorticoid, aldosterone, is produced in the zona glomerulosa of the adrenal cortex - it acts on mineralocorticoid receptors in the kidneys to increase sodium reabsorption and potassium excretion, which in turn helps to regulate plasma electrolyte composition and blood pressure.[T28] In conditions of adrenal insufficiency, such as Addison’s disease, aldosterone is not produced (or is produced in insufficient quantities) and must be replaced by exogenous mineralocorticoids such as fludrocortisone.[A187187] Fludrocortisone binding to mineralocorticoid receptors causes alterations to DNA transcription and translation of proteins that result in an increased density of sodium channels on the apical side of renal tubule cells and an increased density of Na<sup>+</sup>-K<sup>+</sup>-ATPase on the basolateral side.[T28] These increases in receptor density result in increased plasma sodium concentrations, and thus increased blood pressure, as well as a decreased plasma potassium concentration. Fludrocortisone may also exert a direct effect on plasma sodium levels via action at the Na<sup>+</sup>-H<sup>+</sup> exchanger found in the apical membrane of renal tubule cells.[T28] Fludrocortisone also acts on glucocorticoid receptors, albeit with a much lower affinity - the glucocorticoid potency of fludrocortisone is approximately 5-10 times that of endogenous cortisol, whereas its mineralocorticoid potency is 200-400 times greater.[A5423] |
| Targets: | Mineralocorticoid receptor; Glucocorticoid receptor |
| 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 | |
| T47 | Sialin | SLC17A5 | Target is a single protein chain | Q9NRA2 | SLC17A5_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 |