Investigational Drug Details
| Drug ID: | D378 |
| Drug Name: | Troglitazone |
| Synonyms: | Troglitazone |
| Type: | Chemical drug |
| DrugBank ID: | DB00197 |
| DrugBank Description: | Troglitazone was withdrawn in 2000 due to risk of hepatotoxicity. It was superseded by and . |
| PubChem ID: | 5591 |
| CasNo: | 97322-87-7 |
| Repositioning for NAFLD: | Yes |
| SMILES: | CC(C(C)=C1OC(COC2=CC=C(C=C2)CC(C(N3)=O)SC3=O)(C)CCC1=C4C)=C4O |
| Structure: |
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| InChiKey: | GXPHKUHSUJUWKP-UHFFFAOYSA-N |
| Molecular Weight: | 441.549 |
| DrugBank Targets: | Peroxisome proliferator-activated receptor gamma agonist; Long-chain-fatty-acid--CoA ligase 4 inhibitor; Plasminogen activator inhibitor 1 antagonist; Equilibrative nucleoside transporter 1 inhibitor; Estrogen-related receptor gamma inverse agonist; Stero |
| 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. |
| 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 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. |
| Targets: | PPARG agonist; PPARD; PPARA |
| Therapeutic Category: | Improve insulin resistance |
| Clinical Trial Progress: | -- |
| Latest Progress: | Under investigation |
| Trial ID | Source ID | Phases | Status | Study Results | Start Date | Last Update Posted |
|---|
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name | |
|---|---|---|---|---|---|---|---|
| T03 | Peroxisome proliferator-activated receptor alpha | PPARA | agonist | Nuclear hormone receptor | Q07869 | PPARA_HUMAN | Details |
| T04 | Peroxisome proliferator-activated receptor delta | PPARD | agonist | Nuclear hormone receptor | Q03181 | PPARD_HUMAN | Details |
| T05 | Peroxisome proliferator-activated receptor gamma | PPARG | agonist | Nuclear hormone receptor | P37231 | PPARG_HUMAN | Details |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs | |
|---|---|---|---|---|---|
| S08 | Lifestyle measures | Lifestyle intervention; weight loss; diet adaptation; dietary interventions; lifestyle modifications; Exercise | -- | -- | Details |
| S01 | Improve insulin resistance | insulin sensitizer; insulin resistance; glucose tolerance | Biguanide: increases 5-AMP activated protein kinase signaling; SGLT-2 inhibitor; Thiazalidinedione: selective PPAR-γ agonists; GLP-1 agonist | Metformin; Empagliflozin; Canagliflozin; Rosiglitazone; Pioglitazone; Liraglutide | Details |
| S02 | Enhance lipid metabolism | triglyceride-lowering; lipid tolerance; lipid metabolism | 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitor; Decreases intestinal cholesterol absorption; FXR agonist; ACC inhibitor; FAS inhibitor; DGAT2 inhibitor; SCD-1 inhibitor | Atorvastatin; Ezetimibe; Obeticholic Acid; GS-9674; GS-0976; TVB-2640; IONIS-DGAT2rx; Aramchol; | Details |
| Article ID | PMID | Source | Title | |
|---|---|---|---|---|
| A02012 | 34531129 | Dig Liver Dis | Troglitazone inhibits hepatic oval cell proliferation by inducing cell cycle arrest through Hippo/YAP pathway regulation. | Details |
| A07293 | 32553762 | Gastroenterology | Human Pluripotent Stem Cell-Derived Organoids as Models of Liver Disease. | Details |
| A14410 | 29420067 | Am J Physiol Gastrointest Liver Physiol | Organic solute transporter OSTα/β is overexpressed in nonalcoholic steatohepatitis and modulated by drugs associated with liver injury. | Details |
| A22471 | 24534255 | Toxicol Appl Pharmacol | PPAR agonists reduce steatosis in oleic acid-overloaded HepaRG cells. | Details |
| A22551 | 24469900 | Arch Toxicol | A simple transcriptomic signature able to predict drug-induced hepatic steatosis. | Details |
| A24561 | 22749137 | J Nutr Biochem | Lactobacillus casei Shirota protects from fructose-induced liver steatosis: a mouse model. | Details |
| A24915 | 22364184 | J Agric Food Chem | Synergistic effect of cyanidin and PPAR agonist against nonalcoholic steatohepatitis-mediated oxidative stress-induced cytotoxicity through MAPK and Nrf2 transduction pathways. | Details |
| A26709 | 19921118 | Adv Ther | Insulin sensitizers in nonalcoholic fatty liver disease and steatohepatitis: Current status. | Details |
| A27587 | 17983937 | Endocrinol Metab Clin North Am | Use of insulin sensitizers in NASH. | Details |
| A28077 | 16503761 | Expert Opin Investig Drugs | Recent findings concerning thiazolidinediones in the treatment of diabetes. | Details |
| A28479 | 12739988 | Expert Opin Pharmacother | Current best treatment for non-alcoholic fatty liver disease. | Details |
| A28565 | 10902968 | Liver | The role of hepatic peroxisome proliferator-activated receptors (PPARs) in health and disease. | Details |
| A35964 | 19318980 | J Clin Gastroenterol | Thiazolidinediones for the treatment in NASH: sustained benefit after drug discontinuation? | Details |
| A37238 | 16198619 | Hepatol Res | Thiazolidinediones: Pleiotropic drugs with potent anti-inflammatory properties for tissue protection. | Details |
| A38179 | 11965828 | Int J Clin Pract Suppl | Thiazolidinedione hepatotoxicity: a class effect? | Details |
| A38390 | 11374713 | Am J Gastroenterol | Severe cholestatic hepatitis from troglitazone in a patient with nonalcoholic steatohepatitis and diabetes mellitus. | Details |
| A38442 | 11232700 | Am J Gastroenterol | A pilot study of a thiazolidinedione, troglitazone, in nonalcoholic steatohepatitis. | Details |
| A44344 | 28903485 | Toxicol Sci | Editor's Highlight: Mechanistic Toxicity Tests Based on an Adverse Outcome Pathway Network for Hepatic Steatosis. | Details |
| A46743 | 15989845 | Med Clin (Barc) | [Medical management of primary nonalcoholic fatty liver disease]. | Details |
| A48429 | 11232664 | Am J Gastroenterol | Insulin resistance and nonalcoholic steatohepatitis: fat or fiction? | Details |