symmetrically taken indolylmaleimides have been synthesized and their capability to function as GSK 3b inhibitors has been investigated in a human neural BMN 673 ic50 progenitor cell line. On the list of newly synthesized compounds, the substance IM 12 showed a substantial activity in several biological tests that was comparable and sometimes even outplayed the consequences of the known GSK 3b inhibitor SB 216763. Moreover the treating human neural progenitor cells with IM 12 triggered a growth of neuronal cells. Consequently we conclude that indolylmaleimides work via the canonical Wnt signalling pathway by inhibition of the main element enzyme GSK 3b. Wnt signalling is linked to essential cellular processes such as for example cell death, cell polarity, expansion, self-renewal and morphogenic activities. 1 The involvement of Wnt signalling in neural stem-cell differentiation contains elements such as migration, Papillary thyroid cancer 2 synaptogenesis,3 axon guidance4 and neural induction. 5 Wnts constitute a group of 19 secreted glycoproteins which are activators of at least three pathways: one canonical and two non canonical trails and Wnt/Ca2 pathway 6 The canonical pathway is mainly characterized by the stabilization of w catenin in the cytosol. Within an inactive state, w catenin is changed by a complex shaped of Adenomatous Polyposis Coli protein, Axin and Glycogen synthase kinase 3b. 7 Activation of the pathway induces the decay of the degradation complex, stabilizing b catenin which in turn translocates to the nucleus where it binds to the T cell factor /lymphoid booster factor complex and regulates the transcription of Wnt specific target genes. 8,9 purchase IPA-3 The inhibition of the b catenin degradation complex may be accomplished in two ways: both by the binding of a Wnt protein to some complex of low-density lipoprotein receptor and frizzled receptor related protein or by the immediate inhibition of GSK 3b. Up to now, several pharmacological GSK 3 inhibitors have now been described in the literature. The process of inhibition varies from ATP competition, as in the case with paullones, arylindolylmaleimides or indirubins, to Mg2 competition with lithium or beryllium ions. 10,11 Notably, GSK 3 plays a role in several diseases, for example diabetes,12 Alzheimers disease,13 or bi-polar disorders,14 which makes an attractive pharmacological target to it. Yet another interesting aspect could be the influence of canonical Wnt signalling on a few processes linked to proliferation and differentiation of neural precursor cells. The absence of basic fibroblast growth factors enhances neuronal differentiation of neural precursor cells by canonical Wnt signalling. Wnt 3a, 15 Wnt 1 and Wnt 5a regulate proliferation and differentiation of neural precursor cells during dopaminergic neuronal development in the fetal ventral midbrain. 16 neurogenesis is strongly inhibited by GSK 3 deletion. 17 The effect of both, canonical and non canonical Wnt signalling is phase and cellular context dependent.