| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 100mg | |||
| Other Sizes |
| Targets |
Phosphatidylinositol 4-kinase IIIα (PI4KIIIα / PI4KA). GSK-A1 shows selectivity for PI4KIIIα over PI4KIIIβ, PI3Kα, PI3Kβ, and PI3Kδ.
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| ln Vitro |
In HeLa cells, GSK-A1 (100 nM, 30 minutes) decreases HSPA1A's plasma membrane localization [2]. The effects of doxorubicin on leukemia cells are enhanced by GSK-A1 (0-8 μM, 48 hours); in HEK293A cells, GSK-A1 (0-50 nM) promotes the phosphorylation of LATS and YAP [4]. cells (K562/Adr and HL-60/Adr) [3].
GSK-A1 inhibits PI4KIIIα with an IC50 of 3.16 nM. It shows selectivity for PI4KIIIα over PI4KIIIβ, PI3Kα, PI3Kβ, and PI3Kδ with IC50 values >50 nM, but also inhibits PI3Kγ with an IC50 of 15.8 nM. The compound has a pIC50 of 8.5-9.8 for PI4KA inhibition. It effectively reduces PtdIns(4)P levels in cells without affecting PtdIns(4,5)P2. |
| ln Vivo |
In vivo studies for GSK-A1 are primarily focused on anti-HCV research. The compound has shown potential in reducing hepatitis C virus replication in animal models by inhibiting PI4KA activity. Specific in vivo efficacy data including dosing regimens and animal models are limited in publicly available literature.
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| Enzyme Assay |
PI4KIIIα inhibition is assessed using in vitro kinase assays with recombinant PI4KIIIα enzyme and phosphatidylinositol substrate. Radiolabeled ATP or ADP-Glo assays are used to measure kinase activity. IC50 values are calculated from dose-response curves. Selectivity is evaluated by profiling against related lipid kinases including PI4KIIIβ, PI3Kα, PI3Kβ, PI3Kδ, and PI3Kγ.
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| Cell Assay |
Cellular activity is evaluated by measuring PtdIns(4)P and PtdIns(4,5)P2 levels in cells using lipid extraction and mass spectrometry or specific lipid-binding probes. Cells are treated with GSK-A1 at various concentrations, and lipid levels are quantified. Anti-HCV activity is assessed in HCV-infected cell culture models by measuring viral RNA replication.
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| Animal Protocol |
In vivo efficacy for GSK-A1 is evaluated in animal models of HCV infection, such as humanized liver mice or HCV-infected immunodeficient mice. Compound is administered orally or via injection, and viral load is measured over time. Pharmacodynamic markers including PtdIns(4)P levels in liver tissue are assessed.
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| ADME/Pharmacokinetics |
GSK-A1 has a molecular formula of C29H27FN6O4S and a molecular weight of approximately 559 g/mol. It is soluble in DMSO and should be stored at -20°C. Detailed pharmacokinetic parameters such as half-life, oral bioavailability, and plasma protein binding are not extensively characterized in public literature.
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| Toxicity/Toxicokinetics |
Safety data for GSK-A1 indicate it is a research compound for laboratory use only. Specific toxicological profiles including acute toxicity, organ toxicity, and genotoxicity are not extensively published. Standard laboratory safety practices should be followed during handling. The compound contains a sulfonamide group which may pose sensitization risks.
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| References |
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| Additional Infomation |
GSK-A1 is a research tool compound developed by GlaxoSmithKline for studying PI4KIIIα biology. It is not approved for clinical use. The compound has been investigated for anti-HCV potential due to the role of PI4KIIIα in viral replication. GSK-A1 serves as a valuable chemical probe for understanding PI4K signaling pathways.
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| Molecular Formula |
C29H27FN6O4S
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|---|---|
| Molecular Weight |
574.625888109207
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| Exact Mass |
574.179
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| CAS # |
1416334-69-4
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| Related CAS # |
1416334-69-4 GSK-A1
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| PubChem CID |
71116366
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| Appearance |
White to off-white solid powder
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| Density |
1.5±0.1 g/cm3
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| Boiling Point |
829.8±75.0 °C at 760 mmHg
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| Flash Point |
455.7±37.1 °C
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| Vapour Pressure |
0.0±3.0 mmHg at 25°C
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| Index of Refraction |
1.696
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| LogP |
4.18
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
41
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| Complexity |
959
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| Defined Atom Stereocenter Count |
0
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| SMILES |
COC1=C(C=C(C=N1)C2=CC3=C(C=C2)N=C(N3C4=CC=C(C=C4)N5CCOCC5)N)S(=O)(=O)NC6=CC=CC=C6F
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| InChi Key |
AJOGHKUZDLYXKS-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C29H27FN6O4S/c1-39-28-27(41(37,38)34-24-5-3-2-4-23(24)30)17-20(18-32-28)19-6-11-25-26(16-19)36(29(31)33-25)22-9-7-21(8-10-22)35-12-14-40-15-13-35/h2-11,16-18,34H,12-15H2,1H3,(H2,31,33)
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| Chemical Name |
5-[2-amino-3-(4-morpholin-4-ylphenyl)benzimidazol-5-yl]-N-(2-fluorophenyl)-2-methoxypyridine-3-sulfonamide
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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 : ≥ 2 mg/mL (~3.48 mM)
H2O : < 0.1 mg/mL |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 0.2 mg/mL (0.35 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 2.0 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: ≥ 0.2 mg/mL (0.35 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 2.0 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7403 mL | 8.7013 mL | 17.4025 mL | |
| 5 mM | 0.3481 mL | 1.7403 mL | 3.4805 mL | |
| 10 mM | 0.1740 mL | 0.8701 mL | 1.7403 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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