Epigenetic Modulation Using Small Molecules - Targeting Histone Acetyltransferases in Disease.

Area of Science:

• Epigenetics
• Molecular Biology
• Biochemistry

Background:

• Histone acetyltransferases (HATs) and histone deacetylases (HDACs) control cellular acetylation balance, crucial for processes like cell cycle and apoptosis.
• Dysregulated HAT activity is linked to various cancers and neurodegenerative diseases.
• While HDACs are well-characterized therapeutic targets, HATs remain largely unexplored for drug development.

Purpose of the Study:

• To review the role of HATs in disease pathogenesis.
• To summarize the current landscape of HAT inhibitors, including their discovery, optimization, and applications.
• To highlight HATs as potential targets for novel therapeutic strategies.

Main Methods:

• Literature review of HATs, their role in disease, and known inhibitors.
• Analysis of HAT inhibitor discovery, development, and current applications.
• Comparison of HAT and HDAC targeting strategies.

Main Results:

• Aberrant HAT activity is a significant factor in diseases such as prostate, lung, and colon cancers, glioblastomas, and neurodegenerative disorders.
• Despite their disease relevance, HATs have not been actively pursued as therapeutic targets, unlike HDACs.
• A growing number of HAT modulators are being identified, offering potential for drug design.

Conclusions:

• HATs represent a promising, yet underdeveloped, class of therapeutic targets for a range of diseases.
• Further research into HAT inhibitors is crucial for developing novel treatments.
• The development of HAT inhibitors could complement existing HDAC-targeted therapies.