| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 100mg |
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| 250mg | |||
| Other Sizes |
Purity: ≥98%
| Targets |
TNNI3K (troponin I-interacting kinase), also known as cardiac ankyrin repeat kinase (CARK). GSK854 is a potent and highly selective inhibitor of TNNI3K with an IC50 of less than 10 nM. TNNI3K is an essential regulator of cardiac function that has been linked to the progression of dilated cardiomyopathy, cardiac hypertrophy, and ischemia/reperfusion injury. GSK854 exhibits substantial selectivity against B-Raf (>25-fold) and EGFR (IC50 > 25 μM), with >100-fold selectivity over 96% of kinases tested. It also shows activity against ZAK/MLTK when tested at 100 nM.
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| ln Vitro |
GSK854 inhibits TNNI3K with an IC50 of less than 10 nM. In a TNNI3K cellular assay, the compound demonstrates high activity with an IC50 of 8 nM. It exhibits substantial selectivity against B-Raf (>25-fold) and EGFR (IC50 > 25 μM). The compound shows excellent broad-spectrum kinase selectivity with >100-fold selectivity over 96% of kinases tested (≤50% inhibition at 1 μM for 282 of 294 kinases). GSK854 inhibits myocardial infarction-injured cellular pyroptosis and apoptosis in mice.
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| ln Vivo |
GSK854 has been employed as an in vivo tool in investigational studies aimed at defining the role of TNNI3K within heart failure. In mice, GSK854 inhibits myocardial infarction-injured cellular pyroptosis and apoptosis, which may limit oxidative stress, injury, and adverse remodeling in the ischemic heart. The compound demonstrates good pharmacokinetics in rats. These findings support the potential of TNNI3K as a therapeutic target for cardiac disease.
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| Enzyme Assay |
In vitro kinase inhibition assays for GSK854 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 less than 10 nM is determined from the dose-response curve. Selectivity is assessed by testing the compound against a panel of related kinases, including B-Raf and EGFR. The compound demonstrates >100-fold selectivity over 96% of kinases tested.
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| Cell Assay |
In vitro cell-based assays for GSK854 assess its effects on TNNI3K-dependent signaling in cardiac cells or other relevant cell types. Cells are treated with GSK854, and the phosphorylation of downstream targets is measured. The compound shows high activity in a TNNI3K cellular assay with an IC50 of 8 nM. Its effects on cell survival, apoptosis, or other functional endpoints can also be evaluated. The compound is soluble in DMSO at 250 mg/mL.
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| Animal Protocol |
In vivo studies of GSK854 have been conducted in mouse models of myocardial infarction. The compound is administered to mice, and its effects on myocardial infarction-injured cellular pyroptosis and apoptosis are assessed. These studies demonstrate that GSK854 may limit oxidative stress, injury, and adverse remodeling in the ischemic heart. The compound has been employed as an in vivo tool in studies aimed at defining the role of TNNI3K within heart failure.
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| ADME/Pharmacokinetics |
GSK854 demonstrates good pharmacokinetics in rats with the following parameters: clearance (Cl) = 14 mL/min/kg, volume of distribution at steady state (Vdss) = 1.9 L/kg, half-life (t1/2) = 2.3 hours, and oral bioavailability (F) = 48%. The compound has a molecular weight of 482.96 and is soluble in DMSO at 250 mg/mL. It is typically stored as a powder at -20°C for long-term stability.
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| Toxicity/Toxicokinetics |
Specific toxicological data for GSK854 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 and is not for human use.
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| References | |
| Additional Infomation |
GSK854 is a research tool for studying TNNI3K function and its role in cardiac disease. TNNI3K is an essential regulator of cardiac function that has been linked to dilated cardiomyopathy, cardiac hypertrophy, and ischemia/reperfusion injury. GSK854 is a suitable lead for identifying new cardiac medicines and has been employed as an in vivo tool in investigational studies aimed at defining the role of TNNI3K within heart failure. It inhibits myocardial infarction-injured cellular pyroptosis and apoptosis in mice. The compound is not an approved therapeutic agent.
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| Molecular Formula |
C18H19CLN6O4S2
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|---|---|
| Molecular Weight |
482.964259386063
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| Exact Mass |
482.0598
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| CAS # |
1316059-00-3
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| Related CAS # |
1316059-00-3;
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| PubChem CID |
68304261
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| Appearance |
Off-white to light yellow solid powder
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
31
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| Complexity |
788
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1=CN=C(C=C1)NC1=CC(=NC=N1)NC1C=C(C=CC=1S(CC)(=O)=O)S(NC)(=O)=O
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| InChi Key |
OEDGERSSZUMLBI-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H19ClN6O4S2/c1-3-30(26,27)15-6-5-13(31(28,29)20-2)8-14(15)24-17-9-18(23-11-22-17)25-16-7-4-12(19)10-21-16/h4-11,20H,3H2,1-2H3,(H2,21,22,23,24,25)
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| Chemical Name |
3-[6-(5-Chloro-pyridin-2-ylamino)-pyrimidin-4-ylamino]-4-ethanesulfonyl-N-methyl-benzenesulfonamide
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| Synonyms |
GSK854 GSK-854 GSK 854.
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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 |
| 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 : ~250 mg/mL (~517.64 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.31 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 (4.31 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 | 2.0706 mL | 10.3528 mL | 20.7056 mL | |
| 5 mM | 0.4141 mL | 2.0706 mL | 4.1411 mL | |
| 10 mM | 0.2071 mL | 1.0353 mL | 2.0706 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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