Repositioning Candidate Details
| Candidate ID: | R0361 |
| Source ID: | DB00999 |
| Source Type: | approved; vet_approved |
| Compound Type: | small molecule |
| Compound Name: | Hydrochlorothiazide |
| Synonyms: | HCTZ; Hydrochlorothiazide |
| Molecular Formula: | C7H8ClN3O4S2 |
| SMILES: | NS(=O)(=O)C1=C(Cl)C=C2NCNS(=O)(=O)C2=C1 |
| Structure: |
|
| DrugBank Description: | Hydrochlorothiazide is the most commonly prescribed thiazide diuretic. It is indicated to treat edema and hypertension. Hydrochlorothiazide use is common but declining in favour of angiotensin converting enzyme inhibitors. Many combination products are available containing hydrochlorothiazide and angiotensin converting enzyme inhibitors or angiotensin II receptor blockers. Hydrochlorothiazide was granted FDA approval on 12 February 1959. |
| CAS Number: | 58-93-5 |
| Molecular Weight: | 297.739 |
| DrugBank Indication: | Hydrochlorothiazide is indicated alone or in combination for the management of edema associated with congestive heart failure, hepatic cirrhosis, nephrotic syndrome, acute glomerulonephritis, chronic renal failure, and corticosteroid and estrogen therapy. Hydrochlorothiazide is also indicated alone or in combination for the management of hypertension. |
| DrugBank Pharmacology: | Hydrochlorothiazide prevents the reabsorption of sodium and water from the distal convoluted tubule, allowing for the increased elimination of water in the urine. Hydrochlorothiazide has a wide therapeutic window as dosing is individualized and can range from 25-100mg. Hydrochlorothiazide should be used with caution in patients with reduced kidney or liver function. |
| DrugBank MoA: | Hydrochlorothiazide is transported from the circulation into epithelial cells of the distal convoluted tubule by the organic anion transporters OAT1, OAT3, and OAT4. From these cells, hydrochlorothiazide is transported to the lumen of the tubule by multidrug resistance associated protein 4 (MRP4). Normally, sodium is reabsorbed into epithelial cells of the distal convoluted tubule and pumped into the basolateral interstitium by a sodium-potassium ATPase, creating a concentration gradient between the epithelial cell and the distal convoluted tubule that promotes the reabsorption of water. Hydrochlorothiazide acts on the proximal region of the distal convoluted tubule, inhibiting reabsorption by the sodium-chloride symporter, also known as Solute Carrier Family 12 Member 3 (SLC12A3). Inhibition of SLC12A3 reduces the magnitude of the concentration gradient between the epithelial cell and distal convoluted tubule, reducing the reabsorption of water. |
| Targets: | Solute carrier family 12 member 3 inhibitor; Calcium-activated potassium channel subunit alpha-1 inhibitor |
| Inclusion Criteria: | Indication associated |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs |
|---|
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I12 | 10763 | Hypertension | An artery disease characterized by chronic elevated blood pressure in the arteries. https://en.wikipedia.org/wiki/Hypertension, https://www.ncbi.nlm.nih.gov/pubmed/24352797 | disease of anatomical entity/ cardiovascular system disease/vascular disease/ artery disease | Details |