Date published: 2025-9-15

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FCHO2 Inhibitors

FCHO2 inhibitors are a class of chemical compounds that specifically target and modulate the function of the FCHO2 protein, which plays a critical role in clathrin-mediated endocytosis. FCHO2 (F-BAR Domain Containing Protein 2) is an essential component in the initiation of endocytic vesicle formation, particularly at the plasma membrane where it binds to phospholipids and helps in the recruitment of other proteins involved in vesicle scission. By targeting FCHO2, these inhibitors disrupt the early stages of clathrin coat assembly and vesicle budding, which is essential for the internalization of various cargo molecules such as receptors, lipids, and other membrane proteins. The FCHO2 protein works in concert with other key players in the endocytic pathway, including clathrin and adaptor proteins like AP2, so inhibiting FCHO2 can have far-reaching effects on intracellular trafficking and membrane dynamics.

Chemically, FCHO2 inhibitors are diverse, with many structures designed to interact specifically with the F-BAR domain of the protein, preventing its ability to bind membranes or interact with other proteins. These inhibitors often achieve this by blocking the oligomerization or membrane-binding capacity of FCHO2, thereby hindering its function in shaping membranes during vesicle formation. Inhibition of FCHO2 disrupts the local membrane curvature that is necessary for vesicle invagination, ultimately affecting downstream cellular processes such as nutrient uptake, signal transduction, and membrane turnover. Studying FCHO2 inhibitors helps to better understand the molecular details of vesicle formation and endocytic pathways, providing valuable insight into fundamental cellular mechanisms.

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