Repositioning Candidate Details
| Candidate ID: | R0371 |
| Source ID: | DB01016 |
| Source Type: | approved |
| Compound Type: | small molecule |
| Compound Name: | Glyburide |
| Synonyms: | 1-((p-(2-(5-chloro-o-anisamido)ethyl)phenyl)sulfonyl)-3-cyclohexylurea; 1-(p-(2-(5-chloro-2-methoxybenzamido)ethyl)benzenesulfonyl)-3-cyclohexylurea; 5-chloro-N-(2-(4-((((cyclohexylamino)carbonyl)amino)sulfonyl)phenyl)ethyl)-2-methoxybenzamide; Glyburide |
| Molecular Formula: | C23H28ClN3O5S |
| SMILES: | COC1=C(C=C(Cl)C=C1)C(=O)NCCC1=CC=C(C=C1)S(=O)(=O)NC(=O)NC1CCCCC1 |
| Structure: |
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| DrugBank Description: | Glyburide is a second generation sulfonylurea used to treat patients with diabetes mellitus type II. It is typically given to patients who cannot be managed with the standard first line therapy, . Glyburide stimulates insulin secretion through the closure of ATP-sensitive potassium channels on beta cells, raising intracellular potassium and calcium ion concentrations. Glyburide was granted FDA approval on 1 May 1984. A formulation with metformin was granted FDA approval on on 31 July 2000. |
| CAS Number: | 10238-21-8 |
| Molecular Weight: | 494.004 |
| DrugBank Indication: | Glyburide is indicated alone or as part of combination product with metformin, as an adjunct to diet and exercise, to improve glycemic control in adults with type 2 diabetes mellitus. |
| DrugBank Pharmacology: | Glyburide is a second generation sulfonylurea that stimulates insulin secretion through the closure of ATP-sensitive potassium channels on beta cells, raising intracellular potassium and calcium ion concentrations. Glibenclamide has a long duration of action as it is given once daily, and a wide therapeutic index as patients are started at doses as low as 0.75mg but that can increase as high as 10mg or more. Patients taking glyburide should be cautioned regarding an increased risk of cardiovascular mortality as seen with tolbutamide, another sulfonylurea. |
| DrugBank MoA: | Glyburide belongs to a class of drugs known as sulfonylureas. These drugs act by closing ATP-sensitive potassium channels on pancreatic beta cells. The ATP-sensitive potassium channels on beta cells are known as sulfonylurea receptor 1 (SUR1). Under low glucose concentrations, SUR1 remains open, allowing for potassium ion efflux to create a -70mV membrane potential. Normally SUR1 closes in response to high glucose concentrations, the membrane potential of the cells becomes less negative, the cell depolarizes, voltage gated calcium channels open, calcium ions enter the cell, and the increased intracellular calcium concentration stimulates the release of insulin containing granules. Glyburide bypasses this process by forcing SUR1 closed and stimulating increased insulin secretion. |
| Targets: | Sulfonylurea receptor 1, Kir6.2 blocker; ATP-binding cassette sub-family C member 9 modulator; Bile salt export pump inhibitor; ATP-binding cassette sub-family A member 1 inhibitor; Mitochondrial ATP-sensitive potassium channel inhibitor; Carnitine O-palmitoyltransferase 1, liver isoform inhibitor; Cystic fibrosis transmembrane conductance regulator antagonist; Transient receptor potential cation channel subfamily M member 4 inhibitor |
| Inclusion Criteria: | Indication associated |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs | |
|---|---|---|---|---|---|
| S08 | Lifestyle measures | Lifestyle intervention; weight loss; diet adaptation; dietary interventions; lifestyle modifications; Exercise | -- | -- | Details |
| S03 | Anti-fibrosis | fibrosis | Angiotensin Receptor Blocker (ARB); CCR2/CCR5 antagonist; Thyroid receptor β agonist; PEGylated human FGF21 analogue; Monoclonal antibody to lysyl oxidase-like 2 (LOXL2); Galectin-3 inhibitor; FGF19 variant | Losartan; Cenicriviroc; VK-2809; MGL-3196; Pegbelfermin; Simtuzumab; GR-MD-02; NGM282 | Details |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name |
|---|
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I05 | 9352 | Type 2 diabetes mellitus | A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 | disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus | Details |