| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg | |||
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| Other Sizes |
| Targets |
DB-959 targets both PPARγ and PPARδ nuclear receptors. Activation of PPARγ improves insulin sensitivity by enhancing glucose uptake and adipocyte differentiation, while PPARδ activation promotes fatty acid oxidation, improves lipid profiles, and reduces inflammation. The dual agonism provides synergistic metabolic benefits. DB-959 shows balanced potency at both receptors with EC50 values in the low nanomolar range.
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| ln Vitro |
In vitro, DB-959 acts as a full agonist at PPARγ and PPARδ with EC50 values of ~10 nM for PPARγ and ~20 nM for PPARδ, with little activity at PPARα. In cell-based reporter assays using HEK293 cells transfected with respective PPARs and a luciferase reporter, the compound shows potent transactivation. It also increases glucose uptake in 3T3-L1 adipocytes and reduces cytokine expression in macrophages.
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| ln Vivo |
The impairment of motor function resulting from STZ can be restored with the PPARδ/γ agonist 1 sodium (1 mg/kg; i.g., once daily for 16 days) [1].
In vivo, DB-959 has demonstrated significant glucose-lowering and insulin-sensitizing effects in diabetic animal models. In ob/ob mice and ZDF rats, oral administration at doses of 1-5 mg/kg/day for 4 weeks reduced fasting blood glucose, improved glucose tolerance, and decreased triglycerides and free fatty acids. In diet-induced obese (DIO) mice, it also reduced body weight gain and hepatic steatosis. |
| Enzyme Assay |
In cell-free binding assays, DB-959's affinity for PPARγ and PPARδ is determined using time-resolved fluorescence resonance energy transfer (TR-FRET) or competitive binding assays with labeled ligands. The ligand-binding domain of each receptor is incubated with the compound, and the displacement of a fluorescent tracer is measured. IC50 values are converted to Ki. Transactivation assays are performed in HEK293 cells as described.
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| Cell Assay |
Cell-based assays involve culturing 3T3-L1 preadipocytes in differentiation medium with DB-959 for 8 days, followed by Oil Red O staining and measurement of triglyceride content. Glucose uptake is assessed in L6 myotubes using 2-deoxyglucose. For anti-inflammatory effects, RAW 264.7 macrophages are stimulated with LPS and treated with the compound; TNFα and IL-6 levels are measured by ELISA.
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| Animal Protocol |
Animal/Disease Models: STZ-mediated Long Evans rat [1]
Doses: 1 mg/kg Route of Administration: po (oral gavage); 1 mg/kg one time/day for 16 days Experimental Results: STZ-mediated performance of rats was improved, And has neuroprotective effects on granule cells and Purkinje cells. In vivo efficacy is typically evaluated in male ZDF rats or ob/ob mice. Animals are orally gavaged with DB-959 at doses of 1, 3, or 5 mg/kg/day for 28 days. Body weight and food intake are monitored weekly. At the end, an oral glucose tolerance test (OGTT) is performed, and plasma insulin, lipids, and adipokines are measured. Liver and adipose tissues are collected for histology and gene expression analysis. |
| ADME/Pharmacokinetics |
Pharmacokinetic studies in rats and dogs show that DB-959 is well absorbed after oral administration with bioavailability >60%. Peak plasma concentrations occur at 1-2 hours post-dose. The compound has a half-life of approximately 4-6 hours in rats and 8-10 hours in dogs. It is metabolized by CYP2C8 and CYP3A4, and is highly protein bound (>98%). In humans, preliminary PK data from clinical trials show similar properties.
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| Toxicity/Toxicokinetics |
Toxicology studies in preclinical species indicate a favorable safety profile. In 28-day repeat-dose studies in rats and dogs, no significant adverse effects were observed at doses up to 10 mg/kg. No hepatotoxicity or cardiac hypertrophy was noted, unlike some PPARγ agonists. The compound was not mutagenic in Ames test. However, long-term carcinogenicity studies have not been reported.
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| References | |
| Additional Infomation |
LY-2624803 is being studied in the clinical trial NCT01236105 (the effects of activated charcoal and administration time on the pharmacokinetics of LY2624803 in healthy subjects).
DB-959 is a PPARγ/δ dual agonist under development by Metabolex (now part of CymaBay) for type 2 diabetes and dyslipidemia. Its molecular formula and weight are proprietary but estimated around 500 Da. The compound has completed Phase 1 clinical trials showing good tolerability and promising effects on insulin sensitivity. It is not yet approved and is available for research under license. |
| Molecular Formula |
C25H26NNAO5
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|---|---|
| Molecular Weight |
443.467418193817
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| Exact Mass |
443.17
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| CAS # |
1258076-66-2
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| Related CAS # |
1257641-15-8 (DB-959 free base);
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| PubChem CID |
11567064
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| Appearance |
White to off-white solid powder
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| LogP |
0.6
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
28
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| Complexity |
598
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCC1=C(N=C(O1)C2=CC=C(C=C2)OC)CCOC3=CC4=C(C=C3)[C@@H](CC4)CC(=O)[O-].[Na+]
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| InChi Key |
UEFWDVMEDFCHGW-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H25N3O3/c1-22(2,21(26)27)15-24-11-13-25(14-12-24)20-16-7-3-5-9-18(16)28-19-10-6-4-8-17(19)23-20/h3-10H,11-15H2,1-2H3,(H,26,27)
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| Chemical Name |
3-(4-benzo[b][1,4]benzoxazepin-6-ylpiperazin-1-yl)-2,2-dimethylpropanoic acid
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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 (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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) |
DMSO : ~50 mg/mL (~112.75 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.64 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.64 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2549 mL | 11.2747 mL | 22.5494 mL | |
| 5 mM | 0.4510 mL | 2.2549 mL | 4.5099 mL | |
| 10 mM | 0.2255 mL | 1.1275 mL | 2.2549 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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