The chemical class of Msx-3 inhibitors primarily consists of compounds that function as histone deacetylase inhibitors (HDAC inhibitors). These chemicals interfere with the activity of histone deacetylases, enzymes that remove acetyl groups from the lysine residues in histones, leading to a more condensed chromatin structure and generally repressed gene expression. By inhibiting HDACs, these compounds cause an increase in histone acetylation, which is associated with a more open chromatin structure and active transcription. Since Msx-3 is predicted to act upstream of or within the negative regulation of histone acetylation and negative regulation of transcription by RNA polymerase II, the use of HDAC inhibitors can counteract the repressive effects of Msx-3 on gene transcription.
The inhibitors listed range from hydroxamic acid derivatives like Trichostatin A and Suberoylanilide Hydroxamic Acid (SAHA) to short-chain fatty acids like Valproic Acid and Sodium Butyrate. These compounds share the common feature of increasing histone acetylation but differ in their specificity and potency. Some, like RGFP966, are selective for specific HDACs, while others, like Panobinostat, are considered pan-HDAC inhibitors, affecting a broad range of HDAC enzymes. By altering the acetylation status of histones, these inhibitors can interfere with the ability of Msx-3 to maintain a repressive chromatin state, thus indirectly influencing the protein's role in transcription regulation.
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