On 2014 May 04, Jim Woodgett commented:

The somewhat surprising finding here is the apparent cytotoxicity induced by BIO which we and others haven't observed (as noted by the authors) since the original publication by Sato et al (PMID: 14702635 - ref 26). The lack of effects of BIO on Wnt in this paper are largely due to the authors having to use much lower concentrations of BIO (0.5 micromolar) than for the CHIR compounds (5 micromolar) due to the observed cytotoxicity. In our hands, and other studies (e.g. PMID 21295277), there is a strong correlation between induction of beta-catenin, inhibition of GSK-3 and maintenance of pluripotency of ES cells. We'd argue that any selective inhibitors of GSK-3 will activate the canonical Wnt pathway (as well as other pathways negatively regulated by this kinase) but that since greater than 80-90% of total GSK-3 activity must be blocked to observe effects, choice of inhibitors for this purpose will be largely determined by off-target effects. As an aside, lithium is a very poor inhibitor of GSK-3 (ki = 2-3 mM) but is perfectly able to induce beta-catenin signalling and maintain pluripotency. It's also considerably cheaper than most small molecules.

On 2014 May 04, Jim Woodgett commented:

The somewhat surprising finding here is the apparent cytotoxicity induced by BIO which we and others haven't observed (as noted by the authors) since the original publication by Sato et al (PMID: 14702635 - ref 26). The lack of effects of BIO on Wnt in this paper are largely due to the authors having to use much lower concentrations of BIO (0.5 micromolar) than for the CHIR compounds (5 micromolar) due to the observed cytotoxicity. In our hands, and other studies (e.g. PMID 21295277), there is a strong correlation between induction of beta-catenin, inhibition of GSK-3 and maintenance of pluripotency of ES cells. We'd argue that any selective inhibitors of GSK-3 will activate the canonical Wnt pathway (as well as other pathways negatively regulated by this kinase) but that since greater than 80-90% of total GSK-3 activity must be blocked to observe effects, choice of inhibitors for this purpose will be largely determined by off-target effects. As an aside, lithium is a very poor inhibitor of GSK-3 (ki = 2-3 mM) but is perfectly able to induce beta-catenin signalling and maintain pluripotency. It's also considerably cheaper than most small molecules.