Corepressors present many potential avenues for drugs to target a vast range of diseases.
BCL6 upregulation is observed in cancers such as diffuse large B-cell lymphomas (DLBCLs), colorectal cancer, and lung cancer. BCL-6 corepressor, SMRT, NCoR, and other corepressors are able to interact with and transcriptionally repress BCL6. Small-molecule compounds, such as synthetic peptides that target BCL6 and corepressor interactions, as well as other protein-protein interaction inhibitors, have been shown to effectively kill cancer cells.
Activated liver X receptor (LXR) forms a complex with corepressors to suppress the inflammatory response in rheumatoid arthritis, making LXR agonists like GW3965 a potential therapeutic strategy. Ursodeoxycholic acid (UDCA), by upregulating the corepressor small heterodimer partner interacting leucine zipper protein (SMILE), inhibits the expression of IL-17, an inflammatory cytokine, and suppresses Th17 cells, both implicated in rheumatoid arthritis. This effect is dose-dependent in humans, and UCDA is thought to be another prospective agent of rheumatoid arthritis therapy.