TWS119 is a glycogen synthase kinase-3β inhibitor with an IC50 of 30 nM. TWS119 induces neuronal differentiation in pluripotent murine embryonal carcinoma cells and embryonic stem cells (ESCs) at 400 nM.
Biochim Biophys Acta Mol Cell Res. 2018 Oct 12.
|Source||Exp Cell Res (2018). Figure 1. TWS119|
|Method||CFSE proliferation assay|
|Cell Lines||γδT cells|
|Incubation Time||72 h|
|Results||CFSE dilution assays showed that treatment of PBMCs with TWS119 (2 μM) could simulate γδT cells to divide robustly and with less cell apoptosis compared with the control group|
|Cell lines||megakaryocytes (MKs)|
|Preparation method||To examine the inhibitory effects of p38MAPK, PI3K, and GSK-3β on MK differentiation and platelet production, hBMMNCs were cultured in MKLI media in the presence or absence (+/−) of each of the following inhibitors for 12 days: 5 µM SB202190 (AbMole, Houston, TX, USA) to inhibit p38MAPK; 10 µM LY294002 (AbMole, Houston, TX, USA) to inhibit PI3K; and 1 µM TWS119 (AbMole, Houston, TX, USA) to inhibit GSK-3β. To investigate the effect of GSK-3β inhibition on platelet production from mature MKs defined as CD41 (+)/CD42b (+)/propidium iodide (PI, Sigma) (−), as described later (flow cytometry analysis in the Methods), mature MKs were then cultured in MKLI media with TWS119 (+/−) for 6 days.|
|Concentrations||0, 0.17, 1, and 3 µM|
|Incubation time||12 days|
|Animal models||Permanent focal cerebral ischemia rats|
|Formulation||1 % DMSO|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
|Solubility||DMSO 40 mg/mL|
GSK-3β inhibitor TWS119 attenuates rtPA-induced hemorrhagic transformation and activates the Wnt/β-catenin signaling pathway after acute ischemic stroke in rats.
Wang W, et al. Mol Neurobiol. 2016 Dec;53(10):7028-7036. PMID: 26671619.
GSK-3β negatively regulates megakaryocyte differentiation and platelet production from primary human bone marrow cells in vitro.
Ono M, et al. Platelets. 2011;22(3):196-203. PMID: 21231855.
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