PHF21A inhibitors, as listed, primarily focus on modulating epigenetic mechanisms and chromatin structure. These inhibitors do not target PHF21A directly but affect cellular processes and pathways that could indirectly influence PHF21A's function or its downstream effects. The inhibitors mentioned are predominantly histone deacetylase (HDAC) inhibitors, like Vorinostat, Trichostatin A, Panobinostat, Romidepsin, Entinostat, Quisinostat, and Belinostat. HDAC inhibitors function by preventing the removal of acetyl groups from histone proteins, leading to a more open chromatin structure and often an increase in gene expression. Since PHF21A is involved in chromatin remodeling, modifying the histone acetylation status can indirectly influence the genomic regions where PHF21A might exert its effects.
Other inhibitors target DNA methylation processes. Compounds like 5-Azacytidine and Decitabine are inhibitors of DNA methyltransferases. By inhibiting these enzymes, they cause hypomethylation of DNA, potentially altering gene expression patterns. This change can indirectly affect the function or regulation of genes associated with PHF21A activity. A separate class of inhibitors targets the enhancer of zeste homolog 2 (EZH2), part of the Polycomb repressive complex 2 (PRC2), which is involved in histone methylation. Inhibitors like Tazemetostat, GSK126, and CPI-1205 inhibit EZH2, leading to altered histone methylation and consequent changes in gene expression. These modifications can indirectly impact the regulatory networks in which PHF21A is involved.
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