Researchers Identify Small Molecules that Modulate Overactive Receptors Linked to Cancer Development

Researchers at Karolinska Institutet have identified small molecules capable of influencing a hard-to-target receptor family linked to cancer development. The findings have been published inNature Communicationsand theJournal of Biological Chemistry. The human body contains thousands of proteins that act as receivers of various signals. One particular group, the Frizzled receptors, enables cells to communicate and plays a crucial role in tissue growth and repair. However, when these receptors become overactive, they may contribute to the development of cancer. Researchers have therefore long sought ways to modulate them pharmacologically—an endeavor that has proven highly challenging. Researchers at Karolinska Institutet have now investigated Frizzled 7 (FZD7), a receptor essential for intestinal cells and frequently overactive in tumors. By combining large-scale virtual compound libraries, in silico screening and computer simulations with laboratory assays and cryogenic electron microscopy (CryoEM), the team has identified and characterized small molecules that can reduce receptor activity.