| Size | Price | Stock | Qty |
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| 1mg |
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| 10mg |
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| Targets |
GSK2647544 selectively targets the enzyme Lipoprotein-associated phospholipase A2 (Lp-PLA2). Lp-PLA2 circulates in the blood bound to low-density lipoprotein (LDL) and hydrolyzes oxidized phospholipids in LDL to generate lysophosphatidylcholine (LysoPC) and oxidized non-esterified fatty acids, both potent pro-inflammatory mediators. By inhibiting Lp-PLA2, GSK2647544 is a tool to study its role in vascular and neuro-inflammatory diseases.
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| ln Vitro |
In vitro, GSK2647544 is a selective inhibitor of Lp-PLA2. By blocking the activity of Lp-PLA2, the compound is predicted to reduce the generation of pro-inflammatory mediators like lysophosphatidylcholine (LysoPC). This activity is expected to have a broad range of effects on inflammatory signaling pathways, including those implicated in atherosclerosis, stroke, and neurodegenerative diseases. It is primarily secreted by monocyte-derived macrophages.
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| ln Vivo |
In vivo activity data for GSK2647544 is not detailed in the provided sources. As an orally available Lp-PLA2 inhibitor, it is designed to reduce systemic and local inflammation. It has potential applications in neurological research, where Lp-PLA2 activity has been linked to the pathogenesis of diseases such as Alzheimer's disease. Animal studies would be needed to confirm its efficacy in reducing biomarkers of neuroinflammation or atherosclerosis.
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| Enzyme Assay |
The in vitro inhibitory activity of GSK2647544 is determined using a cell-free Lp-PLA2 enzyme activity assay. Recombinant human Lp-PLA2 is incubated in a reaction buffer with varying concentrations of GSK2647544 (e.g., 0.1-1000 nM). The reaction is initiated by the addition of a fluorescent substrate, such as a PAF analog linked to a fluorophore. The hydrolysis of the substrate releases the fluorescent compound, and the increase in fluorescence is measured over time. The IC50 is calculated from the dose-response curve.
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| Cell Assay |
For cellular assays, primary human monocyte-derived macrophages are cultured and differentiated. The cells are pre-incubated with GSK2647544 at various concentrations. The cells are then stimulated to activate Lp-PLA2. The cell supernatant is collected, and the concentration of Lp-PLA2-dependent products, such as lysophosphatidylcholine (LysoPC), is measured by mass spectrometry or an enzymatic assay to quantify the level of target inhibition in a cellular context. Cell viability is assessed via an MTT or LDH assay.
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| Animal Protocol |
In vivo efficacy studies for GSK2647544 could be performed using a mouse model of neuroinflammation, such as LPS-induced neuroinflammation. GSK2647544 would be formulated in a suitable oral vehicle (e.g., 0.5% methylcellulose) and administered orally by gavage to mice at various doses (e.g., 3-30 mg/kg). After a period of treatment, an inflammatory stimulus could be given, and animals would be sacrificed. Brain tissue would be collected to measure levels of Lp-PLA2 activity and its pro-inflammatory products (e.g., LysoPC). Plasma would be collected to measure systemic Lp-PLA2 inhibition and cytokine levels.
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| ADME/Pharmacokinetics |
GSK2647544 is an orally available compound, implying reasonable oral bioavailability. While detailed PK parameters are not provided in the search results, researchers can consult the primary literature for specific data, as it has been developed as a clinical candidate. For in vivo studies, it is typically formulated in a vehicle like 0.5% methylcellulose or a DMSO/PEG300/saline mixture.
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| Toxicity/Toxicokinetics |
Published toxicology data for GSK2647544 is not detailed in the provided sources. As a selective inhibitor, its off-target profile is expected to be manageable. For any in vivo study, researchers would need to conduct a preliminary dose range-finding study to assess acute toxicity. Given its advancement, it likely has a favorable safety profile in preclinical species.
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| References | |
| Additional Infomation |
Lipoprotein-associated phospholipase A2 inhibitor; structure can be found in the first article.
GSK2647544 is a research-grade compound and is not approved for clinical use. It represents an advanced chemical probe for exploring the therapeutic potential of Lp-PLA2 inhibition in inflammatory diseases. Its primary research applications are in the fields of atherosclerosis and neurodegenerative diseases. The compound should be stored as a powder at 4degC, protected from light, or at -20degC for long-term storage. For research use only. |
| Molecular Formula |
C24H18CLF3N4O3
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|---|---|
| Molecular Weight |
502.872934818268
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| Exact Mass |
502.101
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| CAS # |
1380426-95-8
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| PubChem CID |
57336782
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| Appearance |
White to off-white solid powder
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| LogP |
4.9
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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 |
8
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| Heavy Atom Count |
35
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| Complexity |
781
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1(OCCC2=CC=C(OC3=CC=C(Cl)C(C(F)(F)F)=C3)C=C2)=NC=C(CC2=CN=CN=C2)C(=O)N1
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| InChi Key |
DRACNSAQZFZUKW-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H18ClF3N4O3/c25-21-6-5-19(10-20(21)24(26,27)28)35-18-3-1-15(2-4-18)7-8-34-23-31-13-17(22(33)32-23)9-16-11-29-14-30-12-16/h1-6,10-14H,7-9H2,(H,31,32,33)
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| Chemical Name |
2-[2-[4-[4-chloro-3-(trifluoromethyl)phenoxy]phenyl]ethoxy]-5-(pyrimidin-5-ylmethyl)-1H-pyrimidin-6-one
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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: 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)
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| Solubility (In Vitro) |
DMSO: 100 mg/mL (198.86 mM)
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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 | 1.9886 mL | 9.9429 mL | 19.8859 mL | |
| 5 mM | 0.3977 mL | 1.9886 mL | 3.9772 mL | |
| 10 mM | 0.1989 mL | 0.9943 mL | 1.9886 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.
Link: https://clinicaltrials.gov/ct2/show/NCT01924858
Conditions:Alzheimer's DiseaseLink: https://clinicaltrials.gov/ct2/show/NCT01702467
Conditions:Alzheimer's DiseaseLink: https://clinicaltrials.gov/ct2/show/NCT01978327
Conditions:Alzheimer's DiseaseProducts are for research use only; We do not sell to patients
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