UCLA researchers from the Department of Chemistry & Biochemistry have developed a new class of Histone Deacetylase (HDAC) inhibitors that can be tuned for isoform specificity and other properties.
Histone Deacetylase (HDAC) is a ubiquitous enzyme that is involved in epigenetic transcription regulation. As a result, HDAC inhibitors have been proposed as a therapeutic for a variety of conditions including inflammatory disorders, cancers, and neurodegenerative diseases. Despite their ubiquity, there are a large number of different isoforms of HDACs that are dependent on tissue type or organ location. Previous HDAC inhibitors lacked a robust means to selectively target specific isoforms, and therefore had limited ability to be tissue-specific, especially in the brain.
UCLA researchers have developed a new class of carborane-based HDAC inhibitors that can be modified with custom functional groups for tunable isoform specificity. Different diseases are thought to involve unique HDAC isoforms and could be treated by selectively tuning the expression of these compounds, as opposed to being limited to only a crude knock out. This ability to tune isoform specificity also has potential as a research tool for investigating the complex quantitative expressions of HDAC classes. In addition, this new family of carborane-based HDAC inhibitors has demonstrated vastly improved blood-brain-barrier penetration over previous HDAC inhibitors.
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