WDR27 Inhibitors

Chemical inhibitors of WDR27 function primarily by disrupting the Wnt/β-catenin signaling pathway, within which WDR27 operates. Lithium Chloride can inhibit GSK-3β, leading to the stabilization of β-catenin, a key player in Wnt signaling. This alteration in β-catenin levels disrupts the normal transcriptional activity regulated by the pathway, thus affecting WDR27's functional role. Similarly, XAV-939, JW55, and LGK974 target the regulation of β-catenin. XAV-939 inhibits tankyrase, an enzyme crucial for the regulation of the β-catenin destruction complex, further promoting the degradation of β-catenin and affecting WDR27. JW55 also inhibits tankyrase 1 and 2, disrupting WDR27 function by altering Wnt signaling. LGK974 and ETC-159 both inhibit the porcupine enzyme, which is essential for the post-translational processing of Wnt proteins, leading to diminished Wnt signaling and subsequent inhibition of WDR27.

Other inhibitors such as IWR-1, FH535, PKF118-310, CGP049090, iCRT3, iCRT5, and ICG-001 directly target different aspects of the Wnt pathway to inhibit WDR27 function. IWR-1 antagonizes the pathway by stabilizing Axin, promoting β-catenin degradation. FH535 and PKF118-310 disrupt the β-catenin/Tcf4 interaction, a pivotal step in Wnt signaling, thereby inhibiting WDR27. CGP049090 acts as a selective Wnt pathway inhibitor, affecting the pathway's integrity and WDR27's role within it. iCRT3 and iCRT5 disrupt the critical interaction between β-catenin and TCF, leading to pathway inhibition and subsequent functional inhibition of WDR27. Lastly, ICG-001 binds to the CREB-binding protein, preventing its interaction with β-catenin, resulting in the inhibition of the Wnt pathway and the functional role of WDR27. Through these diverse mechanisms, each chemical uniquely disrupts the signaling pathway that is essential for the proper function of WDR27.