the manifold programs for new GSK 3b inhibitors focusing in particular on their application AG-1478 molecular weight in neurodegenerative diseases. A few drugs have now been extensively characterized in this regard. A key element is the GSK 3b inhibitor SB 216763 which can be an indolylmaleimide derivative that acts competitively with ATP and is usually specific to GSK 3b. 18 These features make SB 216763 an interesting lead framework for new active compounds that might inhibit GSK 3b as well. The synthesized derivates are indicated in relation to their inhibitory potential on GSK 3b and the evolving influence on Wnt signalling in human neural progenitor cells. In this research, we used the human NPC line ReNcell VM to investigate the natural purpose of the newly synthesized substances. Especially, this cell line can differentiate into neurons, astrocytes, and oligodendrocytes inside a few days. 19,20 Beside this, the cell line shows a growth and can be cultured easily which makes a suitable model program to it to Plastid test the effect of GSK 3 inhibitors on neuronal differentiation. Moreover only few reports deal with the differentiation of human neuronal progenitor cells. Following from the previous communication on catalytic and stoichiometric activity of low symmetrically replaced 4 indolylmaleimides,21 we here describe in more detail chemical and biological data showing the consequence on Wnt signalling on individual NPCs. Being a major result, one of many new materials showed major biological effects on Wnt signalling within the same range because the identified GSK 3b inhibitor SB 216763. Synthesis of substituted 4 indolylmaleimides Indolylmaleimides 1 7 have already been organized supplier BIX01294 by Pd 2/cataCXium A catalyzed carbonylation of 3 bromo 1 methyl 4 maleimide with carbon monoxide in the existence of alcohols or amines at 90 C. 21 Thus, 3 aminocarbonyl 4 indolylmaleimides and novel 3 alkoxycarbonyl were obtained in 70-90 yield. As an alternative, new 4 amino 3 indolylmaleimides 8 15 have already been synthesized in excellent yields via stoichiometric amination of exactly the same 3 bromo 1 methyl 4 maleimides with corresponding amines. Therapy of ReNcell VM with Kenpaullone, SB 216763 and indolylmaleimides escalates the volume of total b catenin Initially, we investigated whether or not the application of SB 216763 or Kenpaullone to hNPCs could augment the degree of total b catenin. Thus, cells were cultivated under growth conditions until 70-85 confluence before differentiation was induced. The medications were diluted in differentiation medium at appropriate concentrations. Total cell extracts were harvested more than 48 h, to determine the adequate time point for further studies and the amount of total b catenin was calculated utilizing an ELISA specific for human total b catenin. As expected, the change to differentiation condition resulted in a growth of w catenin.