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| Targets |
Edaglitazone primarily targets PPARγ (Peroxisome Proliferator-Activated Receptor Gamma), a nuclear receptor that regulates the expression of genes involved in glucose and lipid metabolism. It is a potent and selective PPARγ agonist, as demonstrated by its EC50 of 35.6 nM for PPARγ cofactor recruitment. This high potency indicates that Edaglitazone binds with high affinity to PPARγ and effectively activates its transcriptional activity. The compound also shows affinity for PPARα, but with a much lower potency (EC50 = 1053 nM), making it highly selective for PPARγ. This selectivity is important for its therapeutic effects, as it allows for the specific modulation of PPARγ-mediated pathways. Upon binding to PPARγ, Edaglitazone induces a conformational change in the receptor, leading to the recruitment of coactivators and the subsequent transcription of target genes. These genes are involved in various processes, including adipocyte differentiation, insulin sensitization, and anti-inflammatory responses. The activation of PPARγ by Edaglitazone enhances insulin sensitivity in obese rats, but not in lean rats, suggesting that its effects are context-dependent and may be influenced by the metabolic state of the organism. In addition to its metabolic effects, Edaglitazone also exhibits antiplatelet activity, which is mediated by an increase in intracellular cAMP levels. This suggests that PPARγ activation may have additional benefits beyond glucose homeostasis, such as cardiovascular protection. The compound is a member of the thiazolidinedione (TZD) class, which are known for their antidiabetic effects through PPARγ activation. Edaglitazone's potent and selective PPARγ agonism makes it a valuable tool for studying the role of this receptor in health and disease.
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| ln Vitro |
Collagen (1.2 μg/mL)-induced platelet aggregation is inhibited by edaglitazone (3–16 μM; 5 min). In a concentration-dependent way, idaglitazone raises intraplatelet cAMP levels. Platelets' levels of PPARγ are not reduced by collagen when idaglitazone is administered [3].
Edaglitazone demonstrates potent in vitro activity as a PPARγ agonist and an antiplatelet agent. In cell-based reporter assays using CV-1 cells expressing murine PPARγ2, Edaglitazone activates PPARγ at concentrations ranging from 0.1 to 1 μM. This activation is mediated through the binding of the compound to PPARγ, leading to the recruitment of coactivators and the transcription of reporter genes. The potency of Edaglitazone for PPARγ cofactor recruitment is demonstrated by its EC50 of 35.6 nM, while its EC50 for PPARα is 1053 nM, indicating high selectivity for PPARγ. In addition to its activity on PPARγ, Edaglitazone exhibits antiplatelet effects in vitro. In platelet aggregation assays, Edaglitazone inhibits platelet aggregation in a concentration-dependent manner. To elucidate the mechanism of its antiplatelet action, the effect of Edaglitazone on intracellular cAMP levels was assessed. Edaglitazone (3, 6, 12 μM) increases intracellular cAMP levels in platelets in a concentration-dependent manner, suggesting that its antiplatelet effect is partially mediated by the modulation of cAMP levels. This is consistent with the known role of cAMP in inhibiting platelet activation. These in vitro findings demonstrate that Edaglitazone is a potent and selective PPARγ agonist with additional antiplatelet activity, making it a compound of interest for the study of diabetes and cardiovascular disease. |
| ln Vivo |
In obese rats, idaglitazone (4.4 mg/kg; administered orally once daily for 10 days) improves insulin sensitivity [2].
Edaglitazone demonstrates significant in vivo activity, primarily by enhancing insulin sensitivity in obese animal models. In studies using obese rats, Edaglitazone enhances insulin sensitivity, an effect that is not observed in lean rats. This suggests that the compound's efficacy is dependent on the presence of insulin resistance, a hallmark of type 2 diabetes and obesity. The enhancement of insulin sensitivity is a key therapeutic effect of PPARγ agonists, as it improves glucose uptake and utilization in peripheral tissues. Edaglitazone displays antidiabetic and anti-hyperglycemic activity in vivo. By activating PPARγ, Edaglitazone promotes the expression of genes involved in glucose and lipid metabolism, leading to improved glycemic control. The compound is orally bioavailable, which is an important feature for its use as a therapeutic agent. In addition to its metabolic effects, Edaglitazone's antiplatelet activity observed in vitro may also translate to in vivo benefits. By increasing cAMP levels in platelets, the compound could potentially reduce the risk of thrombotic events. However, further studies are needed to confirm this effect in vivo. The compound's ability to enhance insulin sensitivity and its oral bioavailability make Edaglitazone a promising candidate for the treatment of type 2 diabetes and obesity. |
| Enzyme Assay |
The in vitro enzyme/receptor binding (non-cellular) assay for Edaglitazone typically involves assessing its affinity for PPARγ and PPARα proteins. A common method is the cofactor recruitment assay, which measures the ability of a compound to promote the interaction between the nuclear receptor and a coactivator peptide. In this assay, purified PPARγ or PPARα protein is incubated with a fluorescently labeled coactivator peptide and varying concentrations of Edaglitazone. The binding of the compound to the receptor induces a conformational change that enhances the recruitment of the coactivator, resulting in an increase in fluorescence polarization or resonance energy transfer. The EC50 for cofactor recruitment is then determined. For Edaglitazone, the EC50 values are 35.6 nM for PPARγ and 1053 nM for PPARα, confirming its potent and selective PPARγ agonism. This assay is crucial for characterizing the compound's binding affinity, selectivity, and efficacy at the molecular level.
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| Cell Assay |
The in vitro cellular assay for Edaglitazone typically involves evaluating its ability to activate PPARγ in a cellular context and its effects on platelet function. To assess PPARγ activation, a reporter gene assay is commonly used. In this assay, cells such as CV-1 are transfected with a plasmid containing a PPARγ expression vector and a reporter gene (e.g., luciferase) under the control of a PPAR response element (PPRE). The cells are then treated with varying concentrations of Edaglitazone, and the reporter gene activity is measured. Edaglitazone activates PPARγ in this assay at concentrations ranging from 0.1 to 1 μM. To evaluate the antiplatelet effect of Edaglitazone, platelet aggregation assays and cAMP measurement assays are performed. Platelets are isolated from whole blood and incubated with Edaglitazone, and aggregation is induced by agonists such as ADP or collagen. The inhibition of aggregation is then measured. Additionally, intracellular cAMP levels in platelets are measured using an ELISA or a similar method. Edaglitazone (3, 6, 12 μM) increases cAMP levels in a concentration-dependent manner, which correlates with its antiplatelet activity. These cellular assays provide functional evidence for Edaglitazone's activity as a PPARγ agonist and an antiplatelet agent.
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| Animal Protocol |
The in vivo animal experimental protocol for Edaglitazone typically involves the use of obese rat models to assess its effects on insulin sensitivity and glycemic control. A common protocol is the hyperinsulinemic-euglycemic clamp study, which is the gold standard for measuring insulin sensitivity in vivo. In this study, obese rats are treated with Edaglitazone orally for a period of time, and then a clamp study is performed to measure the rate of glucose infusion required to maintain euglycemia during a constant insulin infusion. An increase in the glucose infusion rate indicates enhanced insulin sensitivity. Alternatively, an oral glucose tolerance test (OGTT) can be performed, where rats are given an oral glucose load after Edaglitazone treatment, and blood glucose levels are measured over time to assess glucose tolerance. For evaluating the antiplatelet effect, an in vivo model of thrombosis, such as the ferric chloride-induced arterial thrombosis model, can be used. In this model, rats are treated with Edaglitazone, and the time to occlusion of a blood vessel is measured. Edaglitazone is typically administered orally due to its bioavailability. These in vivo models are essential for demonstrating the compound's therapeutic potential and for understanding its mechanism of action in a complex biological system.
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| ADME/Pharmacokinetics |
Edaglitazone is characterized as being orally bioavailable, which is a key pharmacokinetic (PK) property for an antidiabetic agent intended for chronic oral administration. While specific PK parameters such as half-life, clearance, volume of distribution, or maximum concentration (Cmax) are not detailed in the provided references, its oral bioavailability is a critical feature for its therapeutic use. The compound is a thiazolidinedione (TZD) derivative, a class known for their generally favorable PK profiles. Edaglitazone is soluble in DMSO. For in vivo studies, it is typically formulated using a vehicle such as 10% DMSO, 40% PEG300, 5% Tween 80, and 45% saline. The powder formulation is stable when stored at low temperatures. Further studies are needed to fully characterize the PK properties of Edaglitazone, including its absorption, distribution, metabolism, and excretion (ADME) profile.
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| Toxicity/Toxicokinetics |
Specific toxicity (toxicology) data for Edaglitazone, such as LD50 or results from repeat-dose toxicity studies, are not reported in the available literature. However, as a PPARγ agonist of the thiazolidinedione (TZD) class, its toxicity profile would be expected to share some features with other members of this class. Known class-related effects include fluid retention, weight gain, and an increased risk of heart failure. Some TZDs have also been associated with hepatotoxicity and bone fractures. Comprehensive toxicological assessments, including acute and chronic toxicity studies, genotoxicity, and carcinogenicity, would be necessary to fully evaluate the safety profile of Edaglitazone for clinical development. The compound is for research use only and is not intended for human consumption.
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| References |
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| Additional Infomation |
Edaglitazone is a hypoglycemic agent belonging to the thiazide class of antidiabetic drugs. Edaglitazone also appears to lower triglyceride and free fatty acid levels.
Drug Indications It has been studied for the treatment of type 2 diabetes. Edaglitazone is also known as R-483, BM-13.1258, and Edaglitazone sodium. It is a synthetic thiazolidinedione (TZD) compound that functions as a potent agonist of peroxisome proliferator-activated receptor gamma (PPARγ). Its chemical name is 5-[[4-[2-(5-Methyl-2-phenyl-4-oxazolyl)ethoxy]benzo[b]thien-7-yl]methyl]-2,4-thiazolidinedione. The compound has a molecular weight of 464.56 and a purity of ≥98% (HPLC). Edaglitazone enhances insulin sensitivity in obese, but not lean, rats, and displays antidiabetic and anti-hyperglycemic activity. In addition, it shows antiplatelet activity by increasing intracellular cAMP levels. The compound is used in research for diabetes and obesity. It is orally active and has been investigated as a potential therapeutic agent for type 2 diabetes. |
| Molecular Formula |
C24H20N2O4S2
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| Molecular Weight |
464.5566
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| Exact Mass |
464.086
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| CAS # |
213411-83-7
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| Related CAS # |
369631-81-2 (Na);213411-83-7 (free);
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| PubChem CID |
9825701
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| Appearance |
White to off-white solid powder
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| Density |
1.4±0.1 g/cm3
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| Index of Refraction |
1.673
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| LogP |
5.5
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
32
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| Complexity |
689
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1OC(C2C=CC=CC=2)=NC=1CCOC1C2=C(SC=C2)C(CC2SC(=O)NC2=O)=CC=1
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| InChi Key |
HAAXAFNSRADSMK-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H20N2O4S2/c1-14-18(25-23(30-14)15-5-3-2-4-6-15)9-11-29-19-8-7-16(21-17(19)10-12-31-21)13-20-22(27)26-24(28)32-20/h2-8,10,12,20H,9,11,13H2,1H3,(H,26,27,28)
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| Chemical Name |
5-[[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]-1-benzothiophen-7-yl]methyl]-1,3-thiazolidine-2,4-dione
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| Synonyms |
BM-13.1258 RO-2052349-000R-483 Edaglitazone sodiumRO-2052349-602 Ro-205-2349R-483 Edaglitazone
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1526 mL | 10.7629 mL | 21.5257 mL | |
| 5 mM | 0.4305 mL | 2.1526 mL | 4.3051 mL | |
| 10 mM | 0.2153 mL | 1.0763 mL | 2.1526 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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