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Futuristic Approaches Towards Designing of Isozyme-Selective Histone Deacetylase Inhibitors Against Zinc-Dependent Histone Deacetylases

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Histone Deacetylase Inhibitors in Combinatorial Anticancer Therapy

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Abstract

The toxicity issue associated with histone deacetylase inhibitors (HDACi) has been soothed to a greater degree through combinatorial therapeutic strategy. Most of the HDACi being pan-inhibitors often target a broad range of classical HDACs thereby inducing off-target effects. One of the reasons for off-targeting is the high sequence identity at the active sites of classical HDACs. As of now among the four US FDA approved inhibitors three are pan and only one romidepsin is Class I selective. Certain noticeable side effects like thrombocytopenia and fatigue have been reported with pan-HDACi. Due to various aspects of HDACs including the role of specific isozymes in different cancer types it has been hypothesized that intervention with isozyme-selective HDACi may show superior therapeutic index and lesser toxicity. The studies with isozyme-selective inhibitors are ongoing and their enhanced therapeutic benefit is yet to be proved in clinical models. Here I will discuss the different strategies that have been employed for designing isozyme-selective HDACi.

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  1. Division of Basic Sciences and Humanities, Faculty of Agriculture, Wadura Sopore, SKUAST-Kashmir, India

    Shabir Ahmad Ganai

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Ganai, S.A. (2020). Futuristic Approaches Towards Designing of Isozyme-Selective Histone Deacetylase Inhibitors Against Zinc-Dependent Histone Deacetylases. In: Histone Deacetylase Inhibitors in Combinatorial Anticancer Therapy. Springer, Singapore. https://doi.org/10.1007/978-981-15-8179-3_11

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