2. Academic Validation
  3. Paradigm shift of "classical" HDAC inhibitors to "hybrid" HDAC inhibitors in therapeutic interventions

Paradigm shift of "classical" HDAC inhibitors to "hybrid" HDAC inhibitors in therapeutic interventions

  • Eur J Med Chem. 2021 Jan 1:209:112844. doi: 10.1016/j.ejmech.2020.112844.
Gargi Nikhil Vaidya 1,  Pooja Rana 1,  Ashwini Venkatesh 1,  Deep Rohan Chatterjee 1,  Darshan Contractor 2,  Dinesh Parshuram Satpute 1,  Mithilesh Nagpure 1,  Alok Jain 3,  Dinesh Kumar 4
Affiliations

Affiliations

  • 1 Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER) - Ahmedabad, Palaj, Gandhinagar, 382355, Gujarat, India.
  • 2 Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER) - Ahmedabad, Palaj, Gandhinagar, 382355, Gujarat, India.
  • 3 Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER) - Ahmedabad, Palaj, Gandhinagar, 382355, Gujarat, India; Department of Bio-Engineering, Birla Institute of Technology, Mesra, Ranchi, India. Electronic address: alokjain@bitmesra.ac.in.
  • 4 Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER) - Ahmedabad, Palaj, Gandhinagar, 382355, Gujarat, India. Electronic address: dkchem79@gmail.com.
PMID: 33143937 DOI: 10.1016/j.ejmech.2020.112844
Abstract

'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.

Keywords

Anti-cancer agents; Cardiovascular diseases; Combination therapy; HDAC hybrids; Histone deacetylase; Inhibitors; Neurodegenerative disorders.

Figures