| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Targets |
TNNI3K (cardiac troponin I-interacting kinase), also known as cardiac ankyrin repeat kinase (CARK). GSK329 is a potent and selective TNNI3K inhibitor with an IC50 of 10 nM. TNNI3K is a cardiac-specific kinase that has been linked to the progression of dilated cardiomyopathy, cardiac hypertrophy, and ischemia/reperfusion injury.
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| ln Vitro |
GSK329 inhibits TNNI3K with an IC50 of 10 nM. It exhibits selectivity for TNNI3K over human VEGFR2 (40-fold), p38α (80-fold), and B-Raf (>200-fold). It displays >100-fold selectivity over 80% of 185 kinases tested. This high selectivity profile makes GSK329 a valuable tool for studying TNNI3K function specifically.
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| ln Vivo |
In vivo, GSK329 reduces infarct size, ROS levels, and p38 activation in a mouse model of ischemia/reperfusion cardiac injury. This demonstrates significant cardioprotective activity. The compound is orally bioavailable, making it suitable for in vivo studies. These findings support the potential of TNNI3K as a therapeutic target for cardiac injury.
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| Enzyme Assay |
In vitro kinase inhibition assays for GSK329 involve measuring the activity of TNNI3K in the presence of varying concentrations of the compound. The enzyme is incubated with ATP and a substrate peptide, and the phosphorylation of the substrate is quantified. The IC50 value of 10 nM is determined from the dose-response curve. Selectivity is assessed by testing the compound against a panel of related kinases.
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| Cell Assay |
In vitro cell-based assays for GSK329 assess its effects on TNNI3K-dependent signaling in cardiac cells or other relevant cell types. Cells are treated with GSK329, and the phosphorylation of downstream targets is measured by Western blotting or ELISA. The compound's effects on cell survival, apoptosis, or other functional endpoints can also be evaluated. The compound is soluble in DMSO up to 100 mM.
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| Animal Protocol |
In vivo studies of GSK329 have been conducted in a mouse model of ischemia/reperfusion cardiac injury. The compound is administered orally. Endpoints include measurement of infarct size, ROS levels, and p38 activation in cardiac tissue. These studies have demonstrated the cardioprotective effects of TNNI3K inhibition.
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| ADME/Pharmacokinetics |
GSK329 is orally bioavailable. The compound has a molecular weight of 472.25 and is soluble in DMSO up to 100 mM and in ethanol up to 20 mM. It is typically stored at -20°C for long-term stability. Detailed pharmacokinetic parameters such as half-life and Cmax are not extensively reported in the available literature.
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| Toxicity/Toxicokinetics |
Specific toxicological data for GSK329 are not detailed in the available literature. As a research compound, its safety profile has not been comprehensively characterized. Toxicity studies would be required to determine its safety margin and potential off-target effects prior to any clinical application. The compound is for research use only.
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| References | |
| Additional Infomation |
GSK329 is a research tool for studying TNNI3K function and its role in cardiac disease. TNNI3K is a cardiac-specific kinase that has been linked to dilated cardiomyopathy, cardiac hypertrophy, and ischemia/reperfusion injury. The compound is a derivative of the multi-kinase inhibitor sorafenib. It is not an approved therapeutic agent.
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| Molecular Formula |
C19H14CL2F3N5O2
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|---|---|
| Molecular Weight |
472.25
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| Exact Mass |
471.047
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| Elemental Analysis |
C, 48.32; H, 2.99; Cl, 15.01; F, 12.07; N, 14.83; O, 6.78
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| CAS # |
1268490-12-5
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| PubChem CID |
50997674
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| Appearance |
Solid powder
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| LogP |
5.1
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
31
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| Complexity |
591
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CNC1=CC(=NC=N1)OC2=C(C=C(C=C2Cl)NC(=O)NC3=CC=CC(=C3)C(F)(F)F)Cl
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| InChi Key |
QOQADIYOLOHRAW-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H14Cl2F3N5O2/c1-25-15-8-16(27-9-26-15)31-17-13(20)6-12(7-14(17)21)29-18(30)28-11-4-2-3-10(5-11)19(22,23)24/h2-9H,1H3,(H,25,26,27)(H2,28,29,30)
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| Chemical Name |
1-[3,5-dichloro-4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]-3-[3-(trifluoromethyl)phenyl]urea
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| Synonyms |
GSK 329; GSK-329; GSK329
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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 (~211.75 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.40 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 20.8 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: ≥ 2.08 mg/mL (4.40 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 20.8 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 | 2.1175 mL | 10.5876 mL | 21.1752 mL | |
| 5 mM | 0.4235 mL | 2.1175 mL | 4.2350 mL | |
| 10 mM | 0.2118 mL | 1.0588 mL | 2.1175 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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