Inside HDACs with more selective HDAC inhibitors

Joëlle Roche, Philippe Bertrand, European Journal of Medicinal Chemistry, Available online 25 May 2016, ISSN 0223-5234, 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 HDACs biology and structures, this review summarizes the results of the chemists working in this field, and highlights when possible the behaviour of the molecules inside their targets.

Associated disease: Friedreich's ataxia. Partners: Interacts with HDAC7 and HDAC9; DAXX, HDAC10 and DACH1; BCOR, MJD2A/JHDM3A, NRIP1, PRDM6 and SRY, BTBD14B, GLIS2, NR2C1; CBFA2T3 and NKAP; APEX1, MAPK14, ZMYND15, SMRT/NCOR2 and BCL6, INSM1, XBP1 isoform 1, CCAR2, MEF2D, BEND3. Forms a heterologous complex at least with YY1, It may participate in the regulation of transcription through its binding with the zinc-finger transcription factor YY1. Found in a complex with NCOR1 and NCOR2. Component of the N-Cor repressor complex. Component of the Notch corepressor complex. Functions: This protein can also down-regulate p53 function and thus modulate cell growth and apoptosis. This gene is regarded as a potential tumour suppressor gene.

Inside HDACs with more selective HDAC inhibitors