FZD inhibitors: finding the perfect fit
Frizzled (FZD) receptors are key players in a pathway called Wnt that promotes malignant cell growth, making them a promising target for cancer therapy. Despite extensive efforts, identifying truly selective FZD inhibitors that are effective yet safe has been a major challenge in the field.
A new functional assay for selective FZD inhibition
Researchers led by Prof. Vladimir Katanaev have developed a novel functional assay to test the true efficacy of synthetic compounds reported to target FZD receptors. In their , they revealed that only one published compound, the Fz7-21 peptide, acts as a true FZD inhibitor. None of the others were able to inhibit the function of the FZD receptors. Surprisingly, one of the compounds, F7H-28, even quenched firefly luciferase - a common marker in biological assays - rather than targeting an actual biological process.
Of the reported FZD inhibitors, only one compound acts as a true FZD inhibitor. None of the others were able to inhibit the function of FZD receptors. © Adapted from the graphical abstract in Koval et al. 2024.
Potential implications
This research highlights the iterative nature of science and the importance of rigorous testing. While challenges remain, it brings researchers one step closer to more effective FZD-targeted treatments for cancer.