The Wnt signaling pathway plays an important role in a variety of physiological and pathological processes by regulating genes involved in cellular adhesion, proliferation, and differentiation. Many of the key components of the signaling pathway have been elucidated. The Wnt ligand activates downstream signal transduction through interaction with its receptor, Frizzled[3]. BML-284 induces β‐catenin‐ and TCF‐dependent transcriptional activity in a dose‐dependent manner with an EC50 value of 0.7 μM[3]. β‐catenin‐ and TCF‐dependent reporter gene expression induced by BML-284 was blocked in the presence of the dominant negative TCF4, thus suggesting that the active compound functions in the canonical Wnt pathway through the TCFs. In a Xenopus model, embryos treated with BML-284 (n=36) had substantial head defects that ranged from significantly diminished heads and complete loss of eyes, to reduced eyes and heads; the posterior structures of tadpoles remained largely intact. These results suggest that the small‐molecule Wnt agonist indeed mimics the effects of Wnt at the whole‐organism level[3].
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