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| Targets |
GAK ( IC50 = 56 nM )
GAK inhibitor 49 targets cyclin G-associated kinase (GAK), a serine/threonine kinase involved in clathrin-mediated trafficking, cell cycle regulation, and viral entry. It binds to GAK with a Ki of 0.54 nM and inhibits cellular GAK activity with an IC₅₀ of 56 nM. The compound is ATP-competitive and highly selective for GAK over other kinases. GAK inhibitor 49 also shows binding affinity for RIPK2. It exhibits limited inhibition of AAK1, BMP2K, and STK16. |
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| ln Vitro |
Compound 49, also known as GAK inhibitor 49, exhibits a mild inhibitory action on AAK1, BMP2K, and STK16, with IC50 values of >100 μM, 28, 63, and >100 μM, respectively[1].
In vitro, GAK inhibitor 49 demonstrates potent GAK inhibition with a Ki of 0.54 nM and a cellular IC₅₀ of 56 nM. It is more than twice as potent as SGC-GAK-1, which shows an IC₅₀ of 120 nM in HEK293T cellular target engagement assays. The compound exhibits mild inhibitory action on AAK1 (IC₅₀ >100 μM), BMP2K (IC₅₀ = 28 μM), and STK16 (IC₅₀ >100 μM). GAK inhibitor 49 also shows binding to RIPK2. These in vitro characteristics support its use as a highly selective tool for studying GAK biology. |
| ln Vivo |
In vivo data for GAK inhibitor 49 is limited in publicly available sources. As a potent and selective GAK inhibitor with favorable NAK family selectivity, the compound has potential applications in studying clathrin-mediated trafficking, viral infection, and cell cycle regulation in animal models. However, specific published in vivo efficacy studies are not widely reported. GAK inhibitor 49 is primarily used as a research tool for studying GAK function and its role in various cellular processes.
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| Enzyme Assay |
The in vitro GAK inhibition assay for GAK inhibitor 49 uses recombinant GAK enzyme and a peptide substrate in the presence of varying concentrations of the compound. Kinase activity is measured using radioactive (³³P-ATP) or luminescent (ADP-Glo) detection methods, and Ki values are calculated from dose-response curves. Cellular target engagement is assessed in HEK293T cells, where GAK inhibitor 49 is tested at various concentrations and IC₅₀ values are determined. Selectivity profiling against AAK1, BMP2K, and STK16 is performed using similar kinase assay formats.
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| Cell Assay |
Cellular assays for GAK inhibitor 49 are conducted in HEK293T cells to assess target engagement and cellular potency. Cells are treated with varying concentrations of the compound, and GAK inhibition is measured using cellular target engagement assays. IC₅₀ values are calculated from dose-response curves. The compound's effects on clathrin-mediated trafficking, cell cycle progression, and viral entry may be assessed in appropriate cell models. Cell viability and proliferation are measured using standard assays such as MTT or CellTiter-Glo.
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| Animal Protocol |
In vivo studies for GAK inhibitor 49 would typically involve animal models where GAK function is relevant, such as viral infection models or cancer models. The compound would be administered via intraperitoneal or oral routes at doses determined by pharmacokinetic studies. Efficacy would be assessed by measuring relevant disease endpoints. However, specific published in vivo protocols for GAK inhibitor 49 are not available in the current literature. The compound is currently used as a research tool for studying GAK biology.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for GAK inhibitor 49 is not extensively reported in publicly available sources. The compound has a molecular weight of 370.4 g/mol and a molecular formula of C₂₀H₂₂N₂O₅. It is soluble in DMSO at 50-74 mg/mL. The compound has a logP of 3.6. Storage conditions: powder at -20°C for 3 years or 4°C for 2 years; in solvent at -80°C for 6 months or -20°C for 1 month. Detailed PK parameters such as half-life and bioavailability are not available in the current literature.
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| Toxicity/Toxicokinetics |
Toxicity data for GAK inhibitor 49 is limited in publicly available sources. As with all research compounds, GAK inhibitor 49 is intended for research use only and not for human therapeutic applications. Standard in vitro cytotoxicity assays and in vivo tolerability studies would be required for a complete toxicity assessment. The compound's high selectivity for GAK over other kinases suggests a favorable off-target profile, but comprehensive toxicology studies have not been reported.
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| References | |
| Additional Infomation |
GAK inhibitor 49 is a potent, ATP-competitive, and highly selective cyclin G-associated kinase (GAK) inhibitor with a Ki of 0.54 nM and a cellular IC₅₀ of 56 nM. It shows favorable NAK family selectivity with limited inhibition of AAK1, BMP2K, and STK16. The compound also binds to RIPK2. GAK inhibitor 49 is more potent than SGC-GAK-1 (IC₅₀ = 120 nM) in cellular assays. It has a molecular formula of C₂₀H₂₂N₂O₅ and a molecular weight of 370.4 g/mol. GAK inhibitor 49 is a valuable research tool for studying GAK function, clathrin-mediated trafficking, and viral entry mechanisms.
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| Molecular Formula |
C20H22N2O5
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| Molecular Weight |
370.399
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| Exact Mass |
370.15
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| CAS # |
319492-82-5
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| PubChem CID |
5330475
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| Appearance |
White to off-white solid powder
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| LogP |
3.6
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
27
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| Complexity |
440
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| Defined Atom Stereocenter Count |
0
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| SMILES |
COC1C(OC)=CC2=C(C(NC3C=C(OC)C(OC)=C(OC)C=3)=CC=N2)C=1
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| InChi Key |
VYPGLYMWNDRFGZ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H22N2O5/c1-23-16-10-13-14(6-7-21-15(13)11-17(16)24-2)22-12-8-18(25-3)20(27-5)19(9-12)26-4/h6-11H,1-5H3,(H,21,22)
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| Chemical Name |
6,7-dimethoxy-N-(3,4,5-trimethoxyphenyl)quinolin-4-amine
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| Synonyms |
GAK inhibitor 49
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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 : 50~74 mg/mL (135~133.8 mM)
Ethanol : ~6 mg/mL (~16.2 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.62 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 (5.62 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. 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 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. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (5.62 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6998 mL | 13.4989 mL | 26.9978 mL | |
| 5 mM | 0.5400 mL | 2.6998 mL | 5.3996 mL | |
| 10 mM | 0.2700 mL | 1.3499 mL | 2.6998 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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