Repositioning Candidate Details
| Candidate ID: | R0116 |
| Source ID: | DB00412 |
| Source Type: | approved; investigational |
| Compound Type: | small molecule |
| Compound Name: | Rosiglitazone |
| Synonyms: | |
| Molecular Formula: | C18H19N3O3S |
| SMILES: | CN(CCOC1=CC=C(CC2SC(=O)NC2=O)C=C1)C1=CC=CC=N1 |
| Structure: |
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| DrugBank Description: | Rosiglitazone is an anti-diabetic drug in the thiazolidinedione class of drugs. It is marketed by the pharmaceutical company GlaxoSmithKline as a stand-alone drug (Avandia) and in combination with metformin (Avandamet) or with glimepiride (Avandaryl). Like other thiazolidinediones, the mechanism of action of rosiglitazone is by activation of the intracellular receptor class of the peroxisome proliferator-activated receptors (PPARs), specifically PPARγ. Rosiglitazone is a selective ligand of PPARγ, and has no PPARα-binding action. Apart from its effect on insulin resistance, it appears to have an anti-inflammatory effect: nuclear factor kappa-B (NFκB) levels fall and inhibitor (IκB) levels increase in patients on rosiglitazone. Recent research has suggested that rosiglitazone may also be of benefit to a subset of patients with Alzheimer's disease not expressing the ApoE4 allele. This is the subject of a clinical trial currently underway. |
| CAS Number: | 122320-73-4 |
| Molecular Weight: | 357.427 |
| DrugBank Indication: | Rosiglitazone is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. |
| DrugBank Pharmacology: | When rosiglitazone is used as monotherapy, it is associated with increases in total cholesterol, LDL, and HDL. It is also associated with decreases in free fatty acids. Increases in LDL occurred primarily during the first 1 to 2 months of therapy with AVANDIA and LDL levels remained elevated above baseline throughout the trials. In contrast, HDL continued to rise over time. As a result, the LDL/HDL ratio peaked after 2 months of therapy and then appeared to decrease over time. |
| DrugBank MoA: | Rosiglitazone acts as a highly selective and potent agonist at peroxisome proliferator activated receptors (PPAR) in target tissues for insulin action such as adipose tissue, skeletal muscle, and liver. Activation of PPAR-gamma receptors regulates the transcription of insulin-responsive genes involved in the control of glucose production, transport, and utilization. In this way, rosiglitazone enhances tissue sensitivity to insulin. |
| Targets: | Peroxisome proliferator-activated receptor gamma; Long-chain-fatty-acid--CoA ligase 4; Peroxisome proliferator-activated receptor alpha; Peroxisome proliferator-activated receptor delta; Retinoic acid receptor RXR-alpha; Retinoic acid receptor RXR-beta; Retinoic acid receptor RXR-gamma |
| Inclusion Criteria: |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs |
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| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name |
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| 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 |