A study published in *Nature Chemical Biology* (2009) identifies two classes of small molecules that disrupt Wnt signaling pathways, which are crucial for tissue regeneration and cancer. The first class inhibits Porcupine (Porcn), an enzyme essential for Wnt protein production, while the second class disrupts Axin protein turnover, which suppresses Wnt/β-catenin pathway activity. These compounds enable a chemical genetic approach to study Wnt pathway responses and stem cell function in adult tissues. The study demonstrates that these molecules can transiently and reversibly suppress Wnt/β-catenin pathway activity in vivo, offering a mechanism-based strategy to target cancerous cell growth. The findings also suggest that these compounds could be used to broadly manipulate Wnt-independent signaling pathways for chemical genetics and therapeutic purposes. The research highlights the potential of small molecule inhibitors to control Wnt signaling, which is implicated in various diseases, including cancer. The study provides insights into the biochemical mechanisms of Wnt signaling disruption and demonstrates the effectiveness of these compounds in inhibiting Wnt pathway activity in both in vitro and in vivo models. The results suggest that targeting Wnt signaling with small molecules could be a promising therapeutic approach for diseases associated with aberrant Wnt signaling.A study published in *Nature Chemical Biology* (2009) identifies two classes of small molecules that disrupt Wnt signaling pathways, which are crucial for tissue regeneration and cancer. The first class inhibits Porcupine (Porcn), an enzyme essential for Wnt protein production, while the second class disrupts Axin protein turnover, which suppresses Wnt/β-catenin pathway activity. These compounds enable a chemical genetic approach to study Wnt pathway responses and stem cell function in adult tissues. The study demonstrates that these molecules can transiently and reversibly suppress Wnt/β-catenin pathway activity in vivo, offering a mechanism-based strategy to target cancerous cell growth. The findings also suggest that these compounds could be used to broadly manipulate Wnt-independent signaling pathways for chemical genetics and therapeutic purposes. The research highlights the potential of small molecule inhibitors to control Wnt signaling, which is implicated in various diseases, including cancer. The study provides insights into the biochemical mechanisms of Wnt signaling disruption and demonstrates the effectiveness of these compounds in inhibiting Wnt pathway activity in both in vitro and in vivo models. The results suggest that targeting Wnt signaling with small molecules could be a promising therapeutic approach for diseases associated with aberrant Wnt signaling.