TWS119 |
Catalog No.GC17868
One-Click Copy Product Info
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TWS119 is a highly potent and selective inhibitor of glycogen synthase kinase-3β (GSK-3) with KD value of 126nM and IC50 value of 30nM.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 601514-19-6
Sample solution is provided at 25 µL, 10mM.
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TWS119 is a highly potent and selective inhibitor of glycogen synthase kinase-3β (GSK-3) with KD value of 126nM and IC50 value of 30nM[1]. TWS119 exerts neuroprotective and regenerative effects, as well as in directing neural differentiation of stem cells and engineering immune cells[2][4][6][7].
In vitro, TWS119 (5μM) pre-incubation on mouse microglial cell line MG6 cells for 1h before stimulated with PgLPS (1μg/ml) for 48h singificantly decreased mRNA expression of TNF-α and TNF-α secretion induced by PgLPS[3]. TWS119 (20μM, 2.5μM or 5μM) was applied on NK cell line NK-92 or primary NK cells for 48h. NK cells exhibited a significantly increase in degranulation activity, expression of activating receptors, cellular cytotoxicity, and cytokine secretion when co-cultured with human multiple myeloma RPMI8226 cells for 4h[4]. TWS119 (0.5, 1.0, 2.0, 4.0, and 8.0μM) treatment on γδT cells for 72h enhanced the proliferation and survival of γδT cells via activation of the mTOR pathway, upregulation of Bcl-2 expression and inhibition of cleaved caspase-3. TWS119 treatment also upregulated the expression of perforin and granzyme B in γδT cells and enhanced the cytolytic activity of γδT cells against tumour cells[5].
In vivo, TWS119 (30mg/kg) administrated to the neonatal rats by intraperitoneal injection 20min prior to hypoxia-ischemia (HI) procedure performed a neuroprotective function at 7 days after hypoxic-ischemic brain damage via a crosstalk with Wnt/β-catenin and Notch signaling pathways at 24h after hypoxic-ischemic brain damage in neonatal rats[6]. TWS119 (30mg/kg), given intraperitoneally right after rtPA at 4h post-left middle cerebral artery in Sprague–Dawley rats, protects the blood–brain barrier and curbs hemorrhagic transformation by activating Wnt/β-catenin signaling via GSK-3β inhibition[7].
References:
[1] Ding, S. Wu T Y H, Brinker A, et al. Synthetic small molecules that control stem cell fate. 2003.Proc. Natl. Acad. Sci. USA 100, 7632–7637.
[2] Jin F J, Wu Z Z, Hu X, et al. The PI3K/Akt/GSK-3β/ROS/eIF2B pathway promotes breast cancer growth and metastasis via suppression of NK cell cytotoxicity and tumor cell susceptibility. Cancer Biol Med. 2019 Feb;16(1):38-54.
[3] Jiang M Z, Zhang X W, Yan X, et al. GSK3β is involved in promoting Alzheimer's disease pathologies following chronic systemic exposure to Porphyromonas gingivalis lipopolysaccharide in amyloid precursor proteinNL-F/NL-F knock-in mice. Brain Behav Immun. 2021 Nov:98:1-12.
[4] Ren J, Feng X M, Guo Y N, et al. GSK-3β/β-catenin pathway plays crucial roles in the regulation of NK cell cytotoxicity against myeloma cells. FASEB J. 2023 Mar;37(3):e22821.
[5] Chen Y Q, Zheng L, Aldarouish M, et al. Wnt pathway activator TWS119 enhances the proliferation and cytolytic activity of human γδT cells against colon cancer. Exp Cell Res. 2018 Jan 1;362(1):63-71.
[6] Gao L M, Yang L J, Cui H. GSK-3β inhibitor TWS119 alleviates hypoxic-ischemic brain damage via a crosstalk with Wnt and Notch signaling pathways in neonatal rats. Brain Res. 2021 Oct 1:1768:147588.
[7] Wang W, Li M C, Wang Y F, et al. GSK-3β inhibitor TWS119 attenuates rtPA-induced hemorrhagic transformation and activates the Wnt/β-catenin signaling pathway after acute ischemic stroke in rats. Mol Neurobiol. 2016 Dec;53(10):7028-7036.
| Cell experiment [1]: | |
Cell lines | NK cell line NK-92 or primary NK cellson |
Preparation Method | NK cell line NK-92 or primary NK cells were inoculated with TWS119 (2.5μM, 5μM or 20μM) for 48h and then co-cultured with human multiple myeloma RPMI8226 cells for 4h. |
Reaction Conditions | 2.5, 5 or 20μM,; 48h |
Applications | TWS119 concentration-dependently enhanced the degranulation activity, activating-receptor expression, cytotoxicity, and cytokine secretion of NK-92 and primary NK cells when exposed to multiple-myeloma cells. |
| Animal experiment [2]: | |
Animal models | Sprague-Dawley (SD) rat |
Preparation Method | TWS119 was administrated to the neonatal rats by intraperitoneal injection 20min prior to hypoxia-ischemia (HI) procedure (30mg/kg). |
Dosage form | 30mg/kg; i.p.; a single administration |
Applications | TWS119 performed a neuroprotective function at 7 days after hypoxic-ischemic brain damage via a crosstalk with Wnt/β-catenin and Notch signaling pathways at 24h after hypoxic-ischemic brain damage in neonatal rats. |
[1] Ren J, Feng X M, Guo Y N, et al. GSK-3?/?-catenin pathway plays crucial roles in the regulation of NK cell cytotoxicity against myeloma cells. FASEB J. 2023 Mar;37(3):e22821. | |
| Cas No. | 601514-19-6 | SDF | |
| Chemical Name | 3-[[6-(3-aminophenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]oxy]phenol | ||
| Canonical SMILES | C1=CC(=CC(=C1)N)C2=CC3=C(N2)N=CN=C3OC4=CC=CC(=C4)O | ||
| Formula | C18H14N4O2 | M.Wt | 318.33 |
| Solubility | 0.3mg/mL in ethanol, 20mg/mL in DMSO & DMF | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.1414 mL | 15.707 mL | 31.4139 mL |
| 5 mM | 628.3 μL | 3.1414 mL | 6.2828 mL |
| 10 mM | 314.1 μL | 1.5707 mL | 3.1414 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 16 reference(s) in Google Scholar.)