Background:

TWS119 is an inhibitor of glycogen synthase kinase-3β (GSK-3β) with IC50 value of 30nM [1].

TWS119 is screened out from a library of pyrrolopyrimidines as a molecule that selectively induces neuronal differentiation when using mouse P19 EC cells. TWS119 binds to GSK-3β tightly with a Kd value of 126nM and shows an inhibition with IC50 value of 30nM. The combination of TWS119 and GSK-3β modulates the activity of the complex and triggers downstream transcriptional events lead the neuronal induction. Besides that, TWS119 promotes neuronal differentiation of mESCs through another mechanism but not the canonical Wnt signaling pathway [1, 2].

参考文献:
[1] Ding S, Wu T Y H, Brinker A, et al. Synthetic small molecules that control stem cell fate. Proceedings of the National Academy of Sciences, 2003, 100(13): 7632-7637.
[2] Wu T Y H, Ding S. Applying chemical tools to the discovery of novel regenerative medicine. Drug Discovery Today: Technologies, 2006, 3(3): 255-260.