Inside HDACs with more selective HDAC inhibitors

• Published in: European journal of medicinal chemistry Vol. 121; pp. 451 - 483
• Main Authors: Roche, Joëlle, Bertrand, Philippe
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 04.10.2016; Elsevier
• Subjects: Animals; Chemical Sciences; Epigenetics; HDAC inhibitors; Histone acetylation; Histone Deacetylase Inhibitors - chemistry; Histone Deacetylase Inhibitors - metabolism; Histone Deacetylase Inhibitors - pharmacology; Histone Deacetylases - metabolism; Humans; Life Sciences; Molecular modelling; Organic Chemicals - chemistry; Organic Chemicals - metabolism; Organic Chemicals - pharmacology; Substrate Specificity; Synthesis; Epigenetics; HDAC inhibitors; Histone acetylation; Synthesis; Molecular modelling
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2016.05.047

Inhibitors of histone deacetylases (HDACs) are nowadays part of the therapeutic arsenal mainly against cancers, with four compounds approved by the Food and Drug Administration. During the last five years, several groups have made continuous efforts to improve this class of compounds, designing more selective compounds or compounds with multiple capacities. After a survey of the HDAC biology and structures, this review summarizes the results of the chemists working in this field, and highlights when possible the behavior of the molecules inside their targets. Histone deacetylases (HDAC) are involved in cellular processes and the regulation of gene expression through the control of protein acetylation. The deregulation of their expression is correlated to human diseases such as cancers. HDAC inhibitors are nowadays part of the therapeutic arsenal the renormalize the cellular behavior in human tumours. [Display omitted] •Histone deacetylases (HDACs) are epigenetic regulators of protein acetylation.•Abnormal expression of HDACs is involved in human diseases such as cancers.•HDAC inhibitors are used to renormalize protein acetylation in human diseases.•HDAC inhibitor design is mostly oriented toward HDAC selectivity for class members.•Other structural modifications include multi-target activities or imaging modalities.