The chemical class termed BAGE inhibitors encompasses compounds that have the potential to modulate the expression or immunogenicity of BAGE proteins indirectly. These chemicals can affect various cellular pathways including DNA methylation, histone acetylation, protein degradation, and innate and adaptive immune responses. For instance, DNA methyltransferase inhibitors such as Decitabine can induce the re-expression of epigenetically silenced genes, including cancer-testis antigens like BAGE, by promoting the demethylation of DNA. This can result in the enhanced presentation of these antigens to the immune system.
Histone deacetylase inhibitors, such as Trichostatin A, Valproic Acid, Vorinostat, and Sodium Butyrate, can alter chromatin structure, leading to the increased expression of genes like BAGE, and thereby increasing their immunogenicity. This mechanism allows for the possibility of the immune system to better recognize and target tumor cells expressing BAGE proteins. Proteasome inhibitors like Bortezomib can interrupt the degradation of proteins, including aberrant proteins in cancer cells, which can lead to increased presentation of antigens including BAGE on the cell surface, making them more recognizable to the immune system. Alkylating agents such as Dacarbazine and Temozolomide can induce DNA damage in tumor cells, which may lead to an enhanced immune response against tumor-specific antigens. Immunomodulatory agents like IFN-alpha can upregulate the immune response against cancer cells, possibly leading to increased detection and targeting of BAGE-expressing cells. Toll-like receptor agonists such as Poly I:C and Imiquimod can stimulate immune responses and enhance the recognition of BAGE proteins by the immune system.
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