| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
DYRK3 (IC50 = 0.72 nM)
DYRK3 (dual-specificity tyrosine phosphorylation-regulated kinase 3), a member of the DYRK family of kinases. GSK-626616 is a potent and orally bioavailable inhibitor of DYRK3 with an IC50 of 0.7 nM. It also inhibits other members of the DYRK family, including DYRK1A and DYRK2, with similar potency. DYRK3 is involved in the regulation of cell cycle progression, apoptosis, and the cellular stress response. The compound exhibits approximately 20-fold selectivity over casein kinase 2 and negligible activity against a panel of 451 kinases screened, indicating a favorable selectivity profile for studying DYRK family functions. |
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| ln Vitro |
GSK-626616 eliminates the phosphorylation of S6K1 at Thr389 in nonstimulated HeLa cells. In HeLa cells stimulated with insulin and EGF, GSK-626616 decreases the phosphorylation of S6K1 at Thr389, indicating a reduction in mTORC1 activity[2].
In serum-deprived HeLa cells, GSK-626616 decreases the phosphorylation of PRAS40 at Thr246 that is induced by EGF. GSK-626616 enhances PRAS40's binding to mTORC1[2]. GSK-626616 is a potent DYRK3 inhibitor with an IC50 of 0.7 nM. It inhibits other DYRK family members (DYRK1A and DYRK2) with similar potency. In vitro studies demonstrate that GSK-626616 eliminates the phosphorylation of S6K1 at Thr389 in nonstimulated HeLa cells. In HeLa cells stimulated with insulin and EGF, GSK-626616 decreases the phosphorylation of S6K1 at Thr389, indicating a reduction in mTORC1 activity. In serum-deprived HeLa cells, GSK-626616 decreases the phosphorylation of PRAS40 at Thr246 induced by EGF and enhances PRAS40's binding to mTORC1. The compound also exhibits activity against DYRK1A and DYRK2 with similar potency. |
| ln Vivo |
Specific in vivo activity data for GSK-626616 are not extensively detailed in the available literature. As a potent and orally bioavailable DYRK3 inhibitor, it is being investigated as a potential therapy for the treatment of anemia brought on by chemotherapy and functions as a chemoprotective agent. Its oral bioavailability and potent activity against DYRK family kinases make it a promising candidate for in vivo studies targeting DYRK3-related pathways. The compound has been evaluated in a small molecule screening assay using normal human chondrocytes toward osteoarthritis drug discovery.
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| Enzyme Assay |
In vitro enzyme inhibition assays for GSK-626616 involve measuring the activity of DYRK3 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 0.7 nM is determined from the dose-response curve. Selectivity is assessed by testing the compound against a panel of related kinases, including DYRK1A, DYRK2, and casein kinase 2. The compound is an ATP-competitive inhibitor.
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| Cell Assay |
In vitro cell-based assays for GSK-626616 assess its effects on DYRK3-dependent signaling in cultured cells. In HeLa cells, the compound eliminates the phosphorylation of S6K1 at Thr389 in nonstimulated cells and decreases phosphorylation in insulin- and EGF-stimulated cells, indicating a reduction in mTORC1 activity. In serum-deprived HeLa cells, GSK-626616 decreases EGF-induced phosphorylation of PRAS40 at Thr246 and enhances PRAS40's binding to mTORC1. These assays typically use Western blotting to measure phosphorylation of downstream targets. The compound is soluble in DMSO.
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| Animal Protocol |
Specific in vivo animal model protocols for GSK-626616 are not extensively described in the available literature. As an orally bioavailable compound, it would typically be administered by oral gavage in preclinical studies. Its potential as a chemoprotective agent for treating chemotherapy-induced anemia would be evaluated in appropriate animal models. The compound has been used in small molecule screening assays using normal human chondrocytes toward osteoarthritis drug discovery.
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| ADME/Pharmacokinetics |
GSK-626616 is orally bioavailable, making it suitable for in vivo administration. The compound has a molecular weight of 401.27 and a LogP of 4.16. It is soluble in DMSO and is typically stored as a powder at -20°C for long-term stability. Detailed pharmacokinetic parameters such as half-life, Cmax, and AUC are not extensively reported in the available literature but are characteristic of orally bioavailable small molecule kinase inhibitors.
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| Toxicity/Toxicokinetics |
Specific toxicological data for GSK-626616 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 |
GSK-626616 is a research tool for studying DYRK3 function and the role of DYRK family kinases in cell cycle regulation, apoptosis, and cellular stress responses. It is a potential therapy for the treatment of anemia brought on by chemotherapy and functions as a chemoprotective agent. The compound exhibits approximately 20-fold selectivity over casein kinase 2 and negligible activity against a panel of 451 kinases screened. GSK-626616 has been identified in a small molecule screening assay using normal human chondrocytes toward osteoarthritis drug discovery. It is not an approved therapeutic agent.
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| Molecular Formula |
C18H10CL2N4OS
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|---|---|
| Molecular Weight |
401.269199848175
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| Exact Mass |
399.995
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| Elemental Analysis |
C, 53.88; H, 2.51; Cl, 17.67; N, 13.96; O, 3.99; S, 7.99
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| CAS # |
1025821-33-3
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| Related CAS # |
1025821-33-3
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| PubChem CID |
135416229
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.6±0.1 g/cm3
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| Boiling Point |
574.8±60.0 °C at 760 mmHg
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| Flash Point |
301.4±32.9 °C
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| Vapour Pressure |
0.0±1.6 mmHg at 25°C
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| Index of Refraction |
1.755
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| LogP |
4.16
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
26
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| Complexity |
604
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1C=CC=C(C=1/N=C1/NC(/C(=C/C2C=CC3C(C=2)=NC=CN=3)/S/1)=O)Cl
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| InChi Key |
RJPNRXFBYZVRIB-DHDCSXOGSA-N
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| InChi Code |
InChI=1S/C18H10Cl2N4OS/c19-11-2-1-3-12(20)16(11)23-18-24-17(25)15(26-18)9-10-4-5-13-14(8-10)22-7-6-21-13/h1-9H,(H,23,24,25)/b15-9-
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| Chemical Name |
(5Z)-2-(2,6-dichlorophenyl)imino-5-(quinoxalin-6-ylmethylidene)-1,3-thiazolidin-4-one
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| Synonyms |
GSK626616; GSK 626616; GSK-626616
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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: 20~50 mg/mL (49.9~124.6 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (12.46 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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 50.0 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4921 mL | 12.4604 mL | 24.9209 mL | |
| 5 mM | 0.4984 mL | 2.4921 mL | 4.9842 mL | |
| 10 mM | 0.2492 mL | 1.2460 mL | 2.4921 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT00443170 | Completed | Drug: GSK626616, placebo , midazolam Drug: omeprazole, caffeine , flurbiprofen, rosiglitazone |
Healthy Subjects Anaemia |
GlaxoSmithKline | November 2006 | Phase 1 |
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