panHDAC

PanHDAC is a term used in epigenetics and pharmacology to describe inhibitors or activities that broadly target histone deacetylases (HDACs) across multiple isoforms. It is commonly contrasted with isoform-specific HDAC inhibitors, which aim to selectively inhibit a single HDAC family member. The designation panHDAC emphasizes the broad spectrum of enzyme inhibition rather than selectivity for one HDAC.

Histone deacetylases remove acetyl groups from lysine residues on histones and several non-histone proteins, promoting chromatin condensation and transcriptional repression. PanHDAC inhibitors typically bind to the catalytic zinc ion in the HDAC active site, chelate zinc, and prevent deacetylation. Inhibition leads to increased histone acetylation, more open chromatin, and changes in gene expression; non-histone targets can also be affected, influencing processes such as cell cycle control and apoptosis.

Clinical and research use: Pan-HDAC inhibitors have been studied extensively in cancer, where they can arrest cell growth and induce cell death, often in combination with other therapies. Panobinostat is a well-known example of a pan-HDAC inhibitor with activity against multiple HDAC isoforms. Other HDAC inhibitors with broad activity are approved for various indications, though their exact isoform profiles vary. Research also explores panHDAC inhibition in neurodegenerative diseases and inflammatory conditions, though safety and tolerability remain important considerations.

Challenges include dose-limiting toxicities, short-lived responses, and development of resistance. Ongoing work seeks to improve selectivity, identify predictive biomarkers, optimize dosing regimens, and combine panHDAC inhibition with other epigenetic or targeted therapies to enhance efficacy while minimizing adverse effects.