Recent advances in HDAC-based multi-target inhibitors

Histone deacetylase (HDAC) inhibitors have recently been approved for treating hematologic malignancies. Despite this progress, their application in solid tumors remains limited due to insufficient efficacy, high drug resistance, and off-target toxicity. Multi-Target inhibitors offer a promising solution by leveraging synergistic effects to enhance therapeutic outcomes, mitigate drug resistance, and minimize adverse reactions. These inhibitors show considerable potential for advancing treatments for tumors, neurological disorders, inflammatory diseases, and other conditions. This review highlights the latest advancements in HDAC-based multi-target compounds (predominantly dual-target) in recent years, emphasizing target selection, molecular design strategies, structure-activity relationships, and biologicalactivities.