TWS119

Biological Activity

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.

Customer Product Validations & Biological Datas

	Source	Exp Cell Res (2018). Figure 1. TWS119
	Method	CFSE proliferation assay
	Cell Lines	γδT cells
	Concentrations	2 μM
	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

Protocol

Cell Experiment
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 Experiment
Animal models	Permanent focal cerebral ischemia rats
Formulation	1 % DMSO
Dosages	30 mg/kg
Administration	intraperitoneal

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

Species	Mouse	Rat	Rabbit	Guinea pig	Hamster	Dog
Weight (kg)	0.02	0.15	1.8	0.4	0.08	10
Body Surface Area (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km factor	3	6	12	8	5	20

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 K_m factor for a mouse and then divide by the K_m factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Chemical Information

References

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.