Histone deacetylase inhibitors, the small molecules modulating the biological activity of
histone deacetylases are emerging as potent chemotherapeutic agents. Despite their considerable therapeutic
benefits in disease models, the lack of isoform specificity culminates in debilitating off target
effects, raising serious concerns regarding their applicability. This emphasizes the pressing and unmet
medical need of designing isoform selective inhibitors for safe and effective anticancer therapy. Keeping
these grim facts in view, the current article sheds light on structural basis of off-targeting. Furthermore,
the article discusses extensively the role of in silico strategies such as Molecular Docking,
Molecular Dynamics Simulation and Energetically-optimized structure based pharmacophore approach
in designing on-target inhibitors against classical HDACs.
Keywords: HATs, HDACs, HDACi, isoform-selective inhibitors, anticancer therapy, gene expression.
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