Repositioning Candidate Details
| Candidate ID: | R0050 |
| Source ID: | DB00197 |
| Source Type: | approved; investigational; withdrawn |
| Compound Type: | small molecule |
| Compound Name: | Troglitazone |
| Synonyms: | |
| Molecular Formula: | C24H27NO5S |
| SMILES: | CC1=C(C)C2=C(CCC(C)(COC3=CC=C(CC4SC(=O)NC4=O)C=C3)O2)C(C)=C1O |
| Structure: |
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| DrugBank Description: | Troglitazone was withdrawn in 2000 due to risk of hepatotoxicity. It was superseded by [pioglitazone] and [rosiglitazone]. |
| CAS Number: | 97322-87-7 |
| Molecular Weight: | 441.54 |
| DrugBank Indication: | For the treatment of Type II diabetes mellitus. It is used alone or in combination with a sulfonylurea, metformin, or insulin as an adjunct to diet and exercise. |
| DrugBank Pharmacology: | Troglitazone is an oral antihyperglycemic agent which acts primarily by decreasing insulin resistance. Troglitazone is used in the management of type II diabetes (noninsulin-dependent diabetes mellitus (NIDDM) also known as adult-onset diabetes). It improves sensitivity to insulin in muscle and adipose tissue and inhibits hepatic gluconeogenesis. Troglitazone is not chemically or functionally related to either the sulfonylureas, the biguanides, or the g-glucosidase inhibitors. Troglitazone may be used concomitantly with a sulfonylurea or insulin to improve glycemic control. |
| DrugBank MoA: | Troglitazone is a thiazolidinedione antidiabetic agent that lowers blood glucose by improving target cell response to insulin. It has a unique mechanism of action that is dependent on the presence of insulin for activity. Troglitazone decreases hepatic glucose output and increases insulin dependent glucose disposal in skeletal muscle. Its mechanism of action is thought to involve binding to nuclear receptors (PPAR) that regulate the transcription of a number of insulin responsive genes critical for the control of glucose and lipid metabolism. Troglitazone is a ligand to both PPARα and PPARγ, with a highter affinity for PPARγ. The drug also contains an α-tocopheroyl moiety, potentially giving it vitamin E-like activity. Troglitazone has been shown to reduce inflammation, and is associated with a decrase in nuclear factor kappa-B (NF-κB) and a concomitant increase in its inhibitor (IκB). Unlike sulfonylureas, troglitazone is not an insulin secretagogue. |
| Targets: | Peroxisome proliferator-activated receptor gamma; Estrogen-related receptor gamma; Steroid hormone receptor ERR1; Peroxisome proliferator-activated receptor delta; Peroxisome proliferator-activated receptor alpha; Glutathione S-transferase P; Long-chain-fatty-acid--CoA ligase 4; Plasminogen activator inhibitor 1; Equilibrative nucleoside transporter 1 |
| Inclusion Criteria: |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs |
|---|
| 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 |