| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| Targets |
Phosphodiesterase 4 (PDE4). GSK-356278 is a PDE4 inhibitor that prevents the breakdown of cAMP, leading to increased intracellular cAMP levels and anti-inflammatory effects. PDE4 is a key enzyme in inflammatory and immune cells.
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| ln Vitro |
In a competitive filter binding assay using recombinant human PDE4B2B, GSK356278 rivals the enzyme [3H]rolipram expressed in yeast membranes for the high-affinity rolipram binding site (HARBS), with a pKi of 8.6 [1]. HARBS binding has pKi values of 7.9, 7.8, 8.4 and 8.5 in mice, marmosets and ferrets, respectively [1]. With a pIC50 of 7.6, GSK356278 inhibits the release of TNF-α in human whole blood when exposed to LPS[1].
GSK-356278 is a potent PDE4 inhibitor. Specific IC50 values for PDE4 inhibition are not detailed in the available literature. As a PDE4 inhibitor, it would be expected to have anti-inflammatory activity in vitro and in vivo. |
| ln Vivo |
In chewing animals, GSK356278 (0.003-30 mg/kg; po) has anti-inflammatory efficacy without causing pica feeding [1]. In an anxiety model of nonhuman primates, GSK356278 (0.1-0.1 mg/kg; po) has been shown to be effective when exposure conditions do not cause vomiting [1]. Non-human primates that receive GSK356278 (4 dosages, 0.03, 0.1, 0.3, and 1.0 mg/kg for 6 weeks; po) perform better on the object search test [1]. Under an open source license, GSK356278 demonstrated bioavailability (gravity 91%, monkey 23%) and Cmax (gravity 205, monkey 41 nM) (gravity 1, monkey 0.2 mg/kg) [1].
GSK-356278 has been investigated for the treatment of respiratory diseases such as asthma and COPD. It is orally active and has shown efficacy in preclinical models of inflammation. Specific in vivo data are not detailed in the available literature. |
| Enzyme Assay |
In vitro enzyme inhibition assays for GSK-356278 involve measuring the activity of PDE4 in the presence of varying concentrations of the compound. The enzyme is incubated with cAMP substrate, and the hydrolysis of cAMP is quantified. The IC50 is determined from the dose-response curve.
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| Cell Assay |
In vitro cell-based assays for GSK-356278 assess its effects on PDE4 activity and cAMP levels in immune or inflammatory cells. Cells are treated with GSK-356278, and cAMP levels are measured. The compound's anti-inflammatory effects can be assessed by measuring cytokine production.
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| Animal Protocol |
Animal/Disease Models: Male Lewis rats (320-400 g) were treated with lipopolysaccharide (LPS) [1].
Doses: 0.003-3 mg/kg Route of Administration: Oral administration 30 minutes before LPS challenge Experimental Results: diminished neutrophil levels in a dose-dependent manner with an ED50 of 0.09 mg/kg. Animal/Disease Models: Male CD rat [1] Doses: 1 mg/kg (pharmacokinetic/PK/PK analysis) Route of Administration: intravenous (iv) (iv)injection and oral administration Experimental Results: Oral bioavailability (91%), Cmax (205 nM), T1/2 (2.2 h). GSK-356278 has been evaluated in preclinical models of respiratory disease. The compound is typically administered orally, and its effects on airway inflammation, bronchoconstriction, and other endpoints are assessed. Specific protocols are not detailed. |
| ADME/Pharmacokinetics |
GSK-356278 is orally active. As a PDE4 inhibitor, it is expected to have good oral bioavailability. Detailed pharmacokinetic parameters such as half-life, Cmax, and AUC are not extensively reported but are characteristic of PDE4 inhibitors.
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| Toxicity/Toxicokinetics |
Specific toxicological data for GSK-356278 are not detailed in the available literature. PDE4 inhibitors can cause gastrointestinal side effects such as nausea and vomiting. Comprehensive toxicology studies would be required for clinical development.
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| References | |
| Additional Infomation |
Gsk356278 has been used in research on the treatment of anxiety disorders, Huntington's disease, depression, major depressive disorder, and other diseases, as well as in basic scientific trials.
GSK-356278 is a research compound for studying PDE4 function and inflammation. It has been investigated for the treatment of respiratory diseases such as asthma and COPD. It is not an approved therapeutic agent. |
| Molecular Formula |
C21H25N7O2S
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|---|---|
| Molecular Weight |
439.53
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| Exact Mass |
439.179
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| CAS # |
720704-34-7
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| PubChem CID |
10252640
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| Appearance |
White to off-white solid powder
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| LogP |
3.829
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
31
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| Complexity |
598
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
AWDJJMXJUOHGLC-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H25N7O2S/c1-4-28-20-15(11-23-28)19(25-14-5-7-29-8-6-14)16(10-22-20)21-27-26-18(30-21)9-17-12(2)24-13(3)31-17/h10-11,14H,4-9H2,1-3H3,(H,22,25)
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| Chemical Name |
5-[5-[(2,4-dimethyl-1,3-thiazol-5-yl)methyl]-1,3,4-oxadiazol-2-yl]-1-ethyl-N-(oxan-4-yl)pyrazolo[3,4-b]pyridin-4-amine
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| Synonyms |
GSK 356278; GSK356278; GSK-356278
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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. |
| 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 : ~2.5 mg/mL (~5.69 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.25 mg/mL (2.84 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% 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 12.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 1.25 mg/mL (2.84 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 12.5 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. View More
Solubility in Formulation 3: ≥ 1.25 mg/mL (2.84 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2752 mL | 11.3758 mL | 22.7516 mL | |
| 5 mM | 0.4550 mL | 2.2752 mL | 4.5503 mL | |
| 10 mM | 0.2275 mL | 1.1376 mL | 2.2752 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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