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Histone Acetyltransferase Enzymes: From Biological Implications to Most Relevant Inhibitors

  • Daniela TrisciuoglioEmail author
  • Dante RotiliEmail author
Chapter
Part of the Topics in Medicinal Chemistry book series

Abstract

The acetylation of lysine residues of histone and nonhistone proteins is a post-translational modification catalysed by the so-called histone acetyltransferases (HATs) that plays a crucial role in several biological settings. The deregulation of this enzymatic activity is implicated in many disease conditions such as cancer and inflammatory and neurological disorders. Despite many histone acetyltransferase inhibitors (HATi) have been identified so far, there is still the need for new, metabolically stable, more potent and selective HATi as potential therapeutic agents and/or as chemical tools for studying HAT biology. In the present chapter, the main features of HAT enzymes and related diseases have been summarized, with a particular focus on HATi, analysing their structure-activity relationships, mechanisms of action and potential therapeutic applications.

Keywords

Cancer Chemical probes Epigenetics Histone acetyltransferase inhibitors Structure- and ligand-based drug discovery 

Abbreviations

ALL

Acute lymphoid leukaemia

AML

Acute myeloid leukaemia

BRD

Bromodomain

CBP

CREB-binding protein

CSCC

Cutaneous squamous cell carcinoma

DTT

Dithiothreitol

GCN5

General control nonderepressible 5

GNAT

Gcn5-related N-acetyltransferase

HATi

Histone acetyltransferase inhibitors

HATs

Histone acetyltransferases

HDACs

Histone deacetylases

LoCAMs

Long chain alkylidene malonates

LOH

Loss of heterozygosity

MSL

Male-specific lethal

MYST

Moz, Ybf2/Sas3, Sas2, Tip60

NCOA

Nuclear receptor coactivator

NSCLC

Non-small-cell lung cancer

NSL

Non-specific lethal

PCAF

p300/CBP-associated factor

SRC-1

Steroid receptor coactivator-1

SRC-3/AIB-1

Steroid receptor coactivator-3/activated in breast cancer-1

TAFII250

TATA box binding protein (TBP)-associated factor

TIF-2

Transcriptional intermediary factor-2

TRAM-1

Thyroid hormone receptor activator molecule-1

α-TAT1

α-Tubulin acetyltransferase 1

Notes

Compliance with Ethical Standards

Conflict of Interest: The authors declare no conflict of interest.

Ethical Approval: This article does not contain any studies with human participants or animals performed by any of the authors.

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Copyright information

© Springer Nature Switzerland AG  2019

Authors and Affiliations

  1. 1.Institute of Molecular Biology and Pathology, National Research CouncilRomeItaly
  2. 2.Preclinical Models and New Therapeutic Agents UnitIRCCS-Regina Elena National Cancer InstituteRomeItaly
  3. 3.Department of Chemistry and Technologies of DrugsSapienza University of RomeRomeItaly

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