RSC Medicinal Chemistry Blog

This review from Manfred Jung and colleagues looks at the structural biology and inhibition of bromodomains, enzymatic domains which recognise acetylated lysines residues in modified histones in chromatin.  Inhibiting the protein–protein interactions in bromodomains by using small molecules as epigenetic tools is an exciting new area of research, offering potential for new therapeutic approaches.

The review includes:

• Structural features of bromodomains and acetyl-lysine recognition
• Implication of bromodomains in pathological cellular states
• Challenges by targeting protein–protein interactions with small molecules
• Inhibitors of bromodomain-mediated protein–protein interactions
• Inhibitors of the PCAF-BRD/HIV-TatK50ac interaction
• Inhibitors of the CBP-BRD/p53K382ac interaction
• Inhibitors of BET bromodomains

This hot review is part of our forthcoming themed issue on Epigenetics – keep checking back for more hot research in this theme:

Inhibition of bromodomain-mediated protein–protein interactions as a novel therapeutic strategy
Silviya D. Furdas, Luca Carlino, Wolfgang Sippl and Manfred Jung
DOI: 10.1039/C1MD00201E

This hot review from Philip Jones, MD Anderson Cancer Center, Texas, examines our understanding of the structure and function of epigenetic enzymes, including lysine and arginine methyltransferases and demethylases, histone acetyl transferases and histone deacetylases, and the chemical probes and tools available to increase our understanding.

It focuses on the development of a second generation of epigenetic agents able to manipulate histone modifications responsible for aberrant epigenetic gene transcription associated with disease states.

Areas covered:

• Class I and II HDAC inhibitors
• HDAC 1-4, 6, 8 selective inhibitors
• Class III HDAC inhibitors
• Histone acetyl transferase inhibitors
• Histone methyltransferase inhibitors
• Lysine and arginine methyltransferase inhibitors
• Histone demethylase inhibitors
• Lysine specific demethylase 1 inhibitors
• JmJ demethylase inhibitors

Development of second generation epigenetic agents
Philip Jones
DOI: 10.1039/C1MD00199J

This article is part of our forthcoming themed issue on Epigenetics – check back soon for more hot articles in this issue!