| Size | Price | |
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| 500mg | ||
| 1g | ||
| Other Sizes |
Lobeglitazone (CKD-501) is a thiazolidinedione class of antidiabetic agent acting as a potent agonist for both PPARα and PPARγ, working as an insulin sensitizer by binding to the PPAR receptors in fat cells and making the cells more responsive to insulin.
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion
In rat studies, the AUC for the doses 0.5, 1, and 2 mg/kg, AUC values were determined to be 459, 514, and 481 ug min/mL respectively. Absoprtion occurs rapidly after administration, with Tmax of 67.5 and 48.8 min and a Cmax of 0.962 and 0.4.94 ug/mL following doses of 0.5 and 2 mg/kg, respectively. Absolute bioavailability after oral administration was nearly complete and apparently not affected by the dosage; 92.1% following a 0.5 mg/kg dose and 99.0% following a 2 mg/kg dose. Furthermore, the extent of LB remaining in the GI tract at 24 h was found to be negligible, with values less than 0.2% of the oral dose, suggesting that the intestinal absorption is complete in rats at the dose range studied. It has been reported that the combined extent of the excretion of lobeglitazone to the bile, urine and intestine is low (less than 10% of total dose), suggesting that the major route of elimination for the drug involves its metabolism. The steady state volume of distribution (Vss) of lobeglitazone was found to be 189–276 mL/kg. Vss was not found to vary statistically with the dose, suggesting that lobeglitazone follows linear kinetics. In rat studies, systemic clearance was found to be between 1.95 and 2.19 mL/min/kg regardless of dosage. Metabolism / Metabolites Rat studies with lobeglitazone have suggested that it is primarily metabolized by cytochrome P450 (CYP) isozymes, however the exact enzymes involved in its metabolism have yet to be elucidated. The structure of Lobeglitazone's five major metabolites have been characterized along with their pharmacokinetic parameters, and can be seen in the metabolism section below. In rat studies, demethylation and hydroxylation appear to be the primary metabolic pathways. The most abundant metabolite found in these studies was confirmed in vivo as M1, a demethylated derivative of lobeglitazone; its rate of formation was found to be approximately 0.216 ∼ 0.252 mL/min/kg, representing approximately 9.76% of the total lobeglitazone elimination in vivo in rats. Biological Half-Life Following an intravenous dosage of 1 mg/kg, the half life was found to be 110 min. |
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| Toxicity/Toxicokinetics |
Protein Binding
Lobeglitazone was found to bind extensively to plasma proteins (i.e., up to 99.9%) with no appreciable concentration dependency on the unbound fraction. |
| References |
: Safety and efficacy of lobeglitazone monotherapy in patients with type 2 diabetes mellitus over 52 weeks: An open-label extension study. Diabetes Res Clin Pract. 2015 Dec;110(3):e27-30.
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| Additional Infomation |
Lobeglitazone is an aromatic ether.
Lobeglitazone is an antidiabetic medication from the thiazolidinedione class of drugs. It primarily functions as an insulin sensitizer by binding and activating Peroxisome Proliferator-Activated Receptors (PPAR) gamma within fat cells. By activating PPAR-gamma and promoting the binding of insulin at fat cells, lobeglitazone thereby has been shown to reduce blood sugar levels, lower hemoglobain A1C (HbA1C) levels, and improve lipid and liver profiles. Unlike [DB01132], which is a dual PPAR agonist at PPAR-alpha and PPAR-gamma, Lobeglitazone is a pure PPAR-alpha agonist. Lobeglitazone was approved by the Ministry of Food and Drug Safety (South Korea) in 2013, and is being monitored by postmarketing surveillance until 2019. Lobeglitazone is not approved for use by either the Food and Drug Administration (USA), Health Canada, or by the European Medicines Agency for use in the management of diabetes. Lobeglitazone is an agent belonging to the glitazone class of antidiabetic agents with antihyperglycemic activity. Besides its activation of peroxisome proliferator-activated receptor (PPAR) gamma, lobeglitazone is also a potent agonist for PPARalpha. Drug Indication Lobeglitazone was approved by the Ministry of Food and Drug Safety (South Korea) in 2013, and is being monitored by postmarketing surveillance until 2019. Lobeglitazone is not approved for use by either the Food and Drug Administration (USA), Health Canada, or by the European Medicines Agency for use in the management of diabetes. Mechanism of Action Lobeglitazone acts as an insulin sensitizer by binding and activating Peroxisome Proliferator-Activated Receptors (PPAR) gamma within fat cells. By promoting the binding of insulin at fat cells, lobeglitazone has been shown to reduce blood sugar levels, lower hemoglobain A1C (HbA1C) levels, and improve lipid and liver profiles. Unlike [DB01132], which is a dual PPAR agonist at PPAR-alpha and PPAR-gamma, Lobeglitazone is a pure PPAR-alpha agonist. |
| Molecular Formula |
C24H24N4O5S
|
|---|---|
| Molecular Weight |
480.53616
|
| Exact Mass |
480.147
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| CAS # |
607723-33-1
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| Related CAS # |
Lobeglitazone sulfate;763108-62-9
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| PubChem CID |
9826451
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| Appearance |
White to off-white solid powder
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| LogP |
4.015
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| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
9
|
| Rotatable Bond Count |
10
|
| Heavy Atom Count |
34
|
| Complexity |
670
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
CHHXEZSCHQVSRE-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H24N4O5S/c1-28(21-14-22(26-15-25-21)33-19-9-7-17(31-2)8-10-19)11-12-32-18-5-3-16(4-6-18)13-20-23(29)27-24(30)34-20/h3-10,14-15,20H,11-13H2,1-2H3,(H,27,29,30)
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| Chemical Name |
5-(4-(2-((6-(4-methoxyphenoxy)pyrimidin-4-yl)(methyl)amino)ethoxy)benzyl)thiazolidine-2,4-dione
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| Synonyms |
CKD501CKD 501CKD-501
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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 |
| 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 | 2.0810 mL | 10.4050 mL | 20.8099 mL | |
| 5 mM | 0.4162 mL | 2.0810 mL | 4.1620 mL | |
| 10 mM | 0.2081 mL | 1.0405 mL | 2.0810 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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