‘Epigenetic’ regulation of genes via post-translational modulation of proteins is the current mainstay approach for the disease therapies, particularly explored in the Histone Deacetylase (HDAC) class of enzymes. Mainly sight saw in cancer chemotherapeutics, HDAC inhibitors have also found a promising role in other diseases (neurodegenerative disorders, cardiovascular diseases, and viral infections) and successfully entered in various combination therapies (pre-clinical/clinical stages). The prevalent flexibility in the structural design of HDAC inhibitors makes them easily tuneable to merge with other pharmacophore modules for generating multi-targeted single hybrids as a novel tactic to overcome drawbacks of polypharmacy. Herein, we reviewed the putative role of prevalent HDAC hybrids inhibitors in the current and prospective stage as a translational approach to overcome the limitations of the existing conventional drug candidates (parent molecule) when used either alone (drug resistance, solubility issues, adverse side effects, selectivity profile) or in combination (pharmacokinetic interactions, patient compliance) for treating various diseases.

通过基因的“表观”调控蛋白质的翻译后调节是目前疾病治疗的主要方法，特别是在组蛋白脱乙酰基酶（HDAC）类酶中得到了探索。HDAC抑制剂主要用于癌症化学治疗，也已发现其在其他疾病（神经退行性疾病，心血管疾病和病毒感染）中的作用，并成功地进入了各种联合疗法（临床前/临床阶段）。HDAC抑制剂的结构设计具有普遍的灵活性，使其易于调整以与其他药效基团模块融合以生成多靶点单杂交体，从而克服了多药厂的弊端。在这里