Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017;24(37):4121-4150.
doi: 10.2174/0929867324666170223153115.

Epigenetic Modulation Using Small Molecules - _targeting Histone Acetyltransferases in Disease

Andre Richters  1 , Angela N Koehler  1   2
Affiliations

Epigenetic Modulation Using Small Molecules - _targeting Histone Acetyltransferases in Disease

Andre Richters et al. Curr Med Chem. 2017.

Abstract

Histone acetyltransferases (HATs) are epigenetic drivers that catalyze the acetyl transfer from acetyl-CoA to lysines of both histone and non-histone substrates and thereby induce transcription either by chromatin remodeling or direct transcription factor activation. Histone deacetylases (HDACs) conduct the reverse reaction to counter HAT activity. Physiological processes such as cell cycle progression or apoptosis require a thoroughly balanced equilibrium of the interplay between acetylation and deacetylation processes to maintain or, if required, alter the global acetylome status. Aberrant HAT activity has recently been demonstrated to play a crucial role in the progression of various diseases such as prostate, lung, and colon cancers as well as glioblastomas and neurodegenerative diseases. Recent investigations have aimed for the identification of HAT modulators to further decipher the complexity of acetyl transferase related signaling cascades and discover potential leads for drug design approaches. HDACs have been extensively characterized and _targeted by small molecules, including four FDA-approved HDAC inhibitors; in contrast, HATs have not been active _targets for therapeutic development. This review will summarize the status of HAT associated diseases and the arsenal of currently known and available HAT inhibitors with respect to their discovery, further improvements, and current applications.

Keywords: GCN5; Histone acetyltransferases; PCAF; Tip60; cancer; epigenetics; p300/CBP; small molecule inhibitors..

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

LinkOut - more resources

  NODES
twitter 2