| 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 | |||
| Other Sizes |
Purity: ≥98%
| Targets |
TNNI3K (cardiac troponin I-interacting kinase), a member of the tyrosine-like kinase family selectively expressed in heart tissue. GSK-114 is a selective inhibitor of TNNI3K. TNNI3K has been linked to the progression of dilated cardiomyopathy, cardiac hypertrophy, and ischemia/reperfusion injury.
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| ln Vitro |
GSK114 exhibits affinity for seven additional kinases, namely ACK1, B-Raf, GAK, MEK5, PDGFRB, STK36, and ZAK, at a concentration of 1 µM[2].
GSK-114 inhibits TNNI3K with an IC50 of 25 nM. It exhibits a 40-fold selectivity for TNNI3K over B-Raf (IC50 = 1 µM). The compound demonstrates affinity for seven additional kinases (ACK1, B-Raf, GAK, MEK5, PDGFRB, STK36, and ZAK) at a concentration of 1 µM. It has exceptional broad-spectrum kinase selectivity. |
| ln Vivo |
GSK-114 exhibits an excellent oral exposure (poDNAUC=0.18, Cmax=130 ng/ml @ 2 mg/kg, t1/2=3.6 hours, rat Fu =20.2%), offering an ideal balance between specificity and pharmacokinetics[1].
GSK-114 exhibits an excellent oral exposure profile in vivo. At a dose of 2 mg/kg, it achieves a Cmax of 130 ng/mL with an oral AUC (poDNAUC) of 0.18 and a half-life of 3.6 hours in rats. The compound has adequate orally bioavailable exposure to enable its use in cellular and in vivo studies. |
| Enzyme Assay |
In vitro kinase inhibition assays for GSK-114 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 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 GSK-114 assess its effects on TNNI3K-dependent signaling in cardiac cells or other relevant cell types. Cells are treated with GSK-114, and the phosphorylation of downstream targets is measured. The compound's effects on cell survival, proliferation, or other functional endpoints can also be evaluated.
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| Animal Protocol |
In vivo studies of GSK-114 have been conducted in animal models of cardiac disease. The compound is typically administered orally. Specific protocols are not detailed in the available literature, but TNNI3K inhibitors are evaluated in models of dilated cardiomyopathy, cardiac hypertrophy, and ischemia/reperfusion injury using Tnni3k overexpressing or knockout animals.
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| ADME/Pharmacokinetics |
GSK-114 exhibits excellent oral exposure with a half-life of 3.6 hours in rats. At 2 mg/kg oral dose, Cmax is 130 ng/mL, poDNAUC is 0.18, and rat plasma free fraction (Fu) is 20.2%. These properties offer an ideal balance between specificity and pharmacokinetics.
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| Toxicity/Toxicokinetics |
Specific toxicological data for GSK-114 are not detailed in the available literature. As a selective kinase inhibitor, comprehensive toxicology studies would be required to determine its safety margin and potential off-target effects prior to clinical development.
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| References |
[1]. Lawhorn BG, et al. GSK114: A selective inhibitor for elucidating the biological role of TNNI3K. Bioorg Med Chem Lett. 2016;26(14):3355-3358.
[2]. Asquith CRM, et al. New Insights into 4-Anilinoquinazolines as Inhibitors of Cardiac Troponin I-Interacting Kinase (TNNi3K). Molecules. 2020;25(7):1697. Published 2020 Apr 7. |
| Additional Infomation |
GSK-114 is a research tool for elucidating the biological role of TNNI3K. TNNI3K is selectively expressed in heart tissue and has been linked to dilated cardiomyopathy, cardiac hypertrophy, and ischemia/reperfusion injury. The compound is not an approved therapeutic agent but is used to study cardiac disease mechanisms.
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| Molecular Formula |
C19H23N5O4S
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|---|---|
| Molecular Weight |
417.48202252388
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| Exact Mass |
417.147
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| Elemental Analysis |
C, 54.66; H, 5.55; N, 16.78; O, 15.33; S, 7.68
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| CAS # |
1301761-96-5
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| Related CAS # |
1301761-96-5;1301760-19-9 (2HCl);
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| PubChem CID |
52933152
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| Appearance |
Solid powder
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| LogP |
2.4
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
29
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| Complexity |
629
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CNS(=O)(=O)C1=CC(=C(C=C1)N(C)C)NC2=NC=NC3=CC(=C(C=C32)OC)OC
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| InChi Key |
3-((6,7-dimethoxyquinazolin-4-yl)amino)-4-(dimethylamino)-N-methylbenzenesulfonamide
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| InChi Code |
YUSROMRPOFFTMX-UHFFFAOYSA-N
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| Chemical Name |
GSK-114 GSK 114 GSK114.
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| Synonyms |
GSK-114; GSK 114; GSK114.
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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 : ~5.95 mg/mL (~14.25 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 | 2.3953 mL | 11.9766 mL | 23.9532 mL | |
| 5 mM | 0.4791 mL | 2.3953 mL | 4.7906 mL | |
| 10 mM | 0.2395 mL | 1.1977 mL | 2.3953 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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