Modulating the wnt signaling pathway with small molecules

Abstract

Wnt signaling is a critical component during embryonic development and also plays an important role in regulating adult tissue homeostasis. Abnormal activation of Wnt signaling has been implicated in many cancers, while reduced activity of Wnt signaling leads to poor wound healing and structural formations. Thus, extensive efforts have been focused on developing small molecules that have potential to either inhibit or activate the pathway, hoping these molecules can offer leads for novel approaches in treating different human diseases. Many small-molecule inhibitors specifically target various elements, such as Frizzled, Disheveled, Porcupine, or Tankyrase, within the Wnt signaling pathways. These small molecules not only have the potential to be further developed as therapeutic reagents, but they may also be used as chemical probes to dissect the underlying mechanism of the Wnt signaling pathways. Therefore, their respective mechanisms and effective dosages are highly pertinent. Aiming to provide an overview of those molecules in a concise, easy-to-use manner, we summarize and organize the current research on them so that it may be helpful for utilization in different studies.

Decreased microglial Wnt/β-catenin signalling drives microglial pro-inflammatory activation in the developing brain

“…Chelerythrine was purchased from Sigma-Aldrich. To decide on the choice of modulators of Wnt, including considerations for doses and consideration of off target effects we referred to reviews on the subject and previously published works (Fancy et al, 2011;Fancy et al, 2014;Keats et al, 2014;Tran and Zheng, 2017). The L803mts peptide and a scrambled peptide (SCR) were purchased conjugated to short oligonucleotide with disulphide bond linker from BioSynthesis (TX, USA) then hybridized to Cy3-labelled 3DNA at Genisphere (PA, USA).…”

Dishevelled: A masterful conductor of complex Wnt signals

“…The special role of DVL PDZ domain has attracted a lot of attention. Using NMR spectroscopy, various compounds, peptides and antagonists (3289–8625, NSC668036) have been synthesized which could selectively inhibit PDZ-domain interactions to down-regulate the downstream Wnt signaling pathway [11, 48–51]. Interestingly, an anti-tumor inhibitor called FJ9 has been developed which downregulates the canonical Wnt pathway by selectively inhibiting DVL-Fz interaction in human tumor cell lines [52].…”

TRAIL, Wnt, Sonic Hedgehog, TGFβ, and miRNA Signalings Are Potential Targets for Oral Cancer Therapy

“…Many small-molecule inhibitors used to specifically target Wnt signaling proteins, such as Frizzled, Disheveled, Porcupine, or Tankyrase, are well reviewed in terms of effective dosages, Chemical Abstracts Service (CAS) numbers, and targets [ 49 ]. However, their potential application in oral cancer therapy has not been investigated.…”