| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 100mg | |||
| Other Sizes |
| Targets |
Darglitazone targets the nuclear receptor PPARγ, a transcription factor that regulates genes involved in glucose and lipid metabolism. Upon binding, it heterodimerizes with retinoid X receptor (RXR) and binds to PPAR response elements (PPREs) in target gene promoters. This leads to increased expression of genes that promote adipocyte differentiation, fatty acid uptake, and glucose transport (GLUT4), thereby improving insulin sensitivity.
|
|---|---|
| ln Vitro |
Cell lines that mirrored brown (HIB-1B) and white (T3-L1 and 3T3-F442A) adipose tissue and skeletal muscle (L6) were exposed to 30 μM daglitazone for four hours in order to separate the cells. In about 8 hours, increased protein 2 (UCP2) mRNA achieves a plateau of 5–10 times the basal value. Dapglitazone may use PPAR-γ to increase UCP2 gene expression[2].
In vitro, Darglitazone acts as a full agonist of PPARγ with an EC50 in the nanomolar range (e.g., ~100 nM). It induces adipocyte differentiation in 3T3-L1 cells and increases glucose uptake in skeletal muscle cells. It also reduces pro-inflammatory cytokine production in macrophages. The compound shows selectivity for PPARγ over PPARα and PPARδ with minimal cross-reactivity. |
| ln Vivo |
Daglitazone therapy normalizes increased levels of triglycerides, corticosterone, and very-low-density lipoprotein while restoring euglycemia. In ob/ob mice, dapglitazone dramatically decreased the extent of the infarct following a 24-hour recovery period. In diabetic mice, daglitazone treatment dramatically enhances the recovery from hypoxic-ischemic (H/I) injury and reinstates the absent acute brain inflammatory response [1].
In vivo, Darglitazone demonstrates potent glucose-lowering effects in diabetic animal models. In ob/ob mice and Zucker diabetic fatty (ZDF) rats, oral administration at doses of 1-10 mg/kg significantly reduces fasting blood glucose, improves glucose tolerance, and decreases insulin resistance. It also lowers triglyceride and free fatty acid levels. Long-term treatment prevents the development of diabetes in prediabetic models. |
| Enzyme Assay |
In cell-free binding assays, Darglitazone's affinity for PPARγ is measured using a competitive binding assay with tritiated rosiglitazone or a fluorescence polarization assay using purified human PPARγ ligand-binding domain. The compound's binding affinity (Kd) is typically in the low nanomolar range. Transactivation assays are performed in HEK293 cells transfected with a PPARγ expression plasmid and a PPRE-luciferase reporter.
|
| Cell Assay |
Cell-based assays for Darglitazone include adipocyte differentiation assays using 3T3-L1 preadipocytes. Cells are treated with the compound for 48 hours, and differentiation is assessed by Oil Red O staining and measuring triglyceride accumulation. Glucose uptake is measured in L6 myotubes using 2-deoxy-[3H]glucose. Cytokine production in LPS-stimulated RAW 264.7 macrophages is measured by ELISA.
|
| Animal Protocol |
Animal/Disease Models: Male diabetic ob/ob mice [1]
Doses: 1 mg/kg Route of Administration: Oral; daily; 7 days Experimental Results: Blood glucose in diabetic ob/ob mice normalized, circulating triglycerides (TG ) and very low-density lipoprotein (VLDL) were diminished, but had no effect in non-diabetic mice. In vivo efficacy is assessed in genetically diabetic models such as ob/ob mice or ZDF rats. Animals are housed in metabolic cages and treated with Darglitazone by oral gavage at doses of 1, 3, or 10 mg/kg/day for 4-8 weeks. Blood glucose, insulin, and lipid profiles are measured weekly. Oral glucose tolerance tests (OGTT) and insulin tolerance tests (ITT) are performed at the end of the study. Liver and adipose tissues are collected for histology and gene expression analysis. |
| ADME/Pharmacokinetics |
Pharmacokinetic studies in rodents show that Darglitazone is rapidly absorbed after oral administration with a bioavailability of ~70%. Peak plasma concentrations are reached within 1-2 hours, and the half-life is approximately 3-5 hours. The compound is highly protein bound (>99%) and is metabolized by CYP2C8 and CYP3A4. It undergoes enterohepatic recirculation. In humans, similar PK properties were observed.
|
| Toxicity/Toxicokinetics |
Toxicology studies revealed that Darglitazone caused cardiac hypertrophy and edema in rats at high doses, a class effect of TZDs. In chronic studies, it also increased plasma volume and caused mild anemia. Hepatotoxicity was minimal. The compound is not genotoxic. However, due to fluid retention and potential heart failure risk, development was discontinued. It is for research use only.
|
| References |
|
| Additional Infomation |
Darglitazone is a thiazolidinedione antidiabetic drug with hypoglycemic and anti-inflammatory effects. Darglitazone may eliminate acute inflammatory responses in the brain by inhibiting the expression of pro-inflammatory genes.
Darglitazone is a thiazolidinedione PPARγ agonist with molecular formula C23H24N2O4S and molecular weight 424.51. It was developed by Pfizer as CP-86325 but never marketed due to safety concerns. It is used as a research tool for studying PPARγ biology and diabetes. The compound is available for non-clinical research purposes only. |
| Molecular Formula |
C23H20N2O4S
|
|---|---|
| Molecular Weight |
420.4809
|
| Exact Mass |
420.114
|
| Elemental Analysis |
C, 65.70; H, 4.79; N, 6.66; O, 15.22; S, 7.62
|
| CAS # |
141200-24-0
|
| Related CAS # |
Darglitazone Sodium;149904-87-0
|
| PubChem CID |
60870
|
| Appearance |
White to light yellow solid powder
|
| LogP |
4.635
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
30
|
| Complexity |
643
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CC1=C(N=C(O1)C2=CC=CC=C2)CCC(=O)C3=CC=C(C=C3)CC4C(=O)NC(=O)S4
|
| InChi Key |
QQKNSPHAFATFNQ-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C23H20N2O4S/c1-14-18(24-22(29-14)17-5-3-2-4-6-17)11-12-19(26)16-9-7-15(8-10-16)13-20-21(27)25-23(28)30-20/h2-10,20H,11-13H2,1H3,(H,25,27,28)
|
| Chemical Name |
5-[[4-[3-(5-methyl-2-phenyl-1,3-oxazol-4-yl)propanoyl]phenyl]methyl]-1,3-thiazolidine-2,4-dione
|
| Synonyms |
Darglitazone; CP-86325; CP86325; CP 86325; 141200-24-0; darglitazona; DTXSID3057644; AVP9C03Z3K; CP-86,325; CP86,325; CP 86,325;
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO : ~50 mg/mL (~118.9 mM)
|
|---|---|
| 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 | 2.3782 mL | 11.8912 mL | 23.7823 mL | |
| 5 mM | 0.4756 mL | 2.3782 mL | 4.7565 mL | |
| 10 mM | 0.2378 mL | 1.1891 mL | 2.3782 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.
|
|
|
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
