Synthetic approaches and clinical applications of representative HDAC inhibitors for cancer therapy: A review.

Histone deacetylase (HDAC) inhibitors are a promising class of epigenetic modulators in cancer therapy. This review provides a comprehensive analysis of recent synthetic strategies and clinical applications of key HDAC inhibitors for oncology. HDACs play a critical role in modulating chromatin structure and gene expression by removing acetyl groups from histone proteins, leading to transcriptional repression of tumor suppressor genes. By inhibiting HDAC activity, HDAC inhibitors restore normal acetylation patterns, reactivating silenced tumor suppressor genes and inducing cell cycle arrest, apoptosis, and autophagy in cancer cells. The review explores synthetic approaches to developing representative HDAC inhibitors that have been approved or in various clinical trials. Through an integrated perspective on the synthesis, mechanism of action, and clinical advancements of HDAC inhibitors, this review aims to guide future research toward next-generation HDAC inhibitors that could enhance cancer treatment efficacy while minimizing toxicity, offering insights for chemists and clinicians in the field of oncology.