Current HDAC Inhibitors in Clinical Trials

Authors

  • Elisabetta Di Bello Dept. of Drug Chemistry and Technologies, Sapienza University of Rome, Ple. A. Moro 5, 00185 Rome, Italy
  • Beatrice Noce Pasteur Institute, Cenci-Bolognetti Foundation, Sapienza University of Rome, Italy
  • Rossella Fioravanti Dept. of Drug Chemistry and Technologies, Sapienza University of Rome, Ple. A. Moro 5, 00185 Rome, Italy
  • Antonello Mai Pasteur Institute, Cenci-Bolognetti Foundation, Sapienza University of Rome, Italy

DOI:

https://doi.org/10.2533/chimia.2022.448

PMID:

38069716

Keywords:

Cancer, Clinical studies, Epigenetics, Histone deacetylases

Abstract

Epigenetic modifications in eukaryotic biological pathways can lead to the up- or downregulation of regulatory proteins contributing to disease onset and progression. In the last three decades, histone deacetylases (HDACs) are among the most studied epigenetic targets. In fact, aberrant HDAC expression is associated with numerous types of cancer and neurodegenerative disorders, making HDACs promising molecular targets for the design of new drugs. Many HDAC inhibitors (HDACi) are currently in clinical evaluation for various types of cancer, and some of them reached the market after approval by the Food and Drug Administration (FDA). The present review summarizes the various HDAC classes and relative isoforms. Then we discuss different class or isoform-selective HDACi with a strong emphasis on late-stage preclinical candidates and drugs in clinical studies. Last but not least, we shed light on the pharmacokinetic challenges and future directions in HDACi design.

Funding data

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Published

2022-05-25

Issue

Section

Scientific Articles

How to Cite

[1]
E. Di Bello, B. Noce, R. Fioravanti, A. Mai, Chimia 2022, 76, 448, DOI: 10.2533/chimia.2022.448.