GSK 626616 is a novel, potent, and orally bioavailable YAK3/DYRK3 kinase inhibitor with IC50 of 0.7 nM for DYRK3. Possibly used to treat anemia brought on by chemotherapy, it is a chemoprotective agent.
Physicochemical Properties
| Molecular Formula | C18H10CL2N4OS |
| Molecular Weight | 401.269199848175 |
| Exact Mass | 399.995 |
| Elemental Analysis | C, 53.88; H, 2.51; Cl, 17.67; N, 13.96; O, 3.99; S, 7.99 |
| CAS # | 1025821-33-3 |
| Related CAS # | 1025821-33-3 |
| PubChem CID | 135416229 |
| Appearance | Light yellow to yellow solid powder |
| Density | 1.6±0.1 g/cm3 |
| Boiling Point | 574.8±60.0 °C at 760 mmHg |
| Flash Point | 301.4±32.9 °C |
| Vapour Pressure | 0.0±1.6 mmHg at 25°C |
| Index of Refraction | 1.755 |
| LogP | 4.16 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 2 |
| Heavy Atom Count | 26 |
| Complexity | 604 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | ClC1C=CC=C(C=1/N=C1/NC(/C(=C/C2C=CC3C(C=2)=NC=CN=3)/S/1)=O)Cl |
| InChi Key | RJPNRXFBYZVRIB-DHDCSXOGSA-N |
| 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- |
| Chemical Name | (5Z)-2-(2,6-dichlorophenyl)imino-5-(quinoxalin-6-ylmethylidene)-1,3-thiazolidin-4-one |
| Synonyms | GSK626616; GSK 626616; GSK-626616 |
| HS Tariff Code | 2934.99.9001 |
| 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) |
Biological Activity
| Targets | DYRK3 (IC50 = 0.72 nM) |
| 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]. |
| References |
[1]. GSK626616: A DYRK3 Inhibitor as a Potential New Therapy for the Treatment of Anemia. Blood 2007 110:510; [2]. Dual specificity kinase DYRK3 couples stress granule condensation/dissolution to mTORC1 signaling. Cell. 2013;152(4):791-805. |
Solubility Data
| Solubility (In Vitro) | DMSO: 20~50 mg/mL (49.9~124.6 mM) |
| 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 |