University of Dundee

CLS Researchers make drug discovery breakthrough

27 Aug 2014

The potential to develop new drugs to target a class of enzymes implicated in major diseases such as cancer and neurodegenerative conditions has been boosted with the development of a new drug discovery method in a research effort led by the University of Dundee.
The research group have been examining the class of enzymes called deubiquitylases (DUBs). Around 90 DUBs have been identified in the human genome and they are active in almost every process in cells.
Drugs that target components of the ubiquitin system are predicted to become of major importance to the pharmaceutical industry in the future. However, until now it has proved difficult to carry out sufficiently detailed and accurate mass testing of compounds against specific DUBs.
Now the team led by Dr Matthias Trost in the Medical Research Council Protein Phosphorylation and Ubiquitylation Unit (MRC-PPU) at Dundee have developed a new drug discovery method that will allow greater analysis of the activity of specific DUBs and how they react to treatment with drug compounds.
The results of the research are published today in Nature Communications.
The work has been carried out with collaborators at Harvard Medical School in Boston, the University of Glasgow and the Beatson Institute for Cancer Research.
“This is the first method which allows us to carry out high-throughput screening of DUBs, which is essential if we are going to be able to identify new drug targets and develop new drugs,” said Dr Trost.
“The major pharmaceutical companies, many of whom we work with, are very excited about this because it opens new avenues of drug development in this area. DUBs are tricky to work with because they can appear very similar and little is known about their functions.
“With this method we have developed we can reliably test compounds and identify specific inhibitors, which is absolutely crucial.”
Dundee is among the world’s leading centres for research into phosphorylation and ubiquitylation, areas which are becoming increasingly important in determining how abnormalities in cellular proteins can affect our health.
The MRC-PPU was established in 1990 by the MRC to investigate the role that protein phosphorylation play in regulating human diseases and originally comprised two research groups and less than 20 staff.  It was led by Sir Philip Cohen for 21 years until he was succeeded in April 2012 by Professor Dario Alessi. The Unit comprises nearly 20 major research groups and over 150 staff.
Its researchers have published over 500 research papers that have greatly contributed to our understanding of a variety of human diseases such as cancer, diabetes, immune disorders and neurodegeneration.