LEDGF Inhibitors

LEDGF inhibitors are a class of chemical compounds that specifically target the protein Lens Epithelium-Derived Growth Factor (LEDGF), also known as p75. LEDGF is a transcription coactivator that is involved in a variety of cellular processes, including gene regulation and protection of cells from stress-induced damage. It is particularly known for its role in binding chromatin and interacting with a variety of cellular and viral proteins. LEDGF interacts with Integrase, a viral enzyme, through its integrase-binding domain (IBD), promoting its tethering to the chromatin. This interaction is crucial for certain biological processes, making LEDGF an attractive target for inhibition to disrupt specific pathways related to DNA interaction and binding. LEDGF inhibitors work by disrupting this interaction, usually by binding to the IBD, thereby blocking its role in protein-protein interactions.

Chemically, LEDGF inhibitors can take various structural forms, including small molecules with heterocyclic cores that are capable of forming strong hydrogen bonds or hydrophobic interactions with the integrase-binding domain of LEDGF. These inhibitors may contain functional groups like amines, carboxyls, or aromatic rings that enhance their affinity for LEDGF through hydrogen bonding or π-π stacking interactions. Some inhibitors are designed to interfere with LEDGF's DNA binding ability by altering its interaction with the chromatin. By disrupting these interactions, LEDGF inhibitors can affect the stability and localization of proteins that rely on LEDGF for chromatin association. Researchers studying LEDGF inhibitors often explore diverse chemical libraries to optimize the structural properties of these molecules for specific molecular interactions with LEDGF.