Scientists Develop Protein ‘Map' For Identifying New Cancer Drugs
By C. Rajan, contributing writer
Scientists at Imperial College London recently uncovered how a disease-causing enzyme can make changes to proteins, and in turn, were able to develop a protein map to identify inhibitors for the enzyme.
The enzyme, N-myristoyltransferase (NMT), is known to make irreversible changes to proteins and is implicated in many diseases including cancer, epilepsy, and Alzheimer's disease. Targeting this enzyme and blocking its activity could potentially lead to new treatments for cancer and inflammatory conditions.
Professor Ed Tate, lead researcher, Department of Chemistry at Imperial College London, said, "We now have a much fuller picture of how NMT operates, and more importantly, how it can be inhibited, than ever before. This is the first time that we have been able to look in molecular detail at how this potential drug target works within an entire living cancer cell, so this is a really exciting step forward for us."
The researchers developed a specialized set of tools to identify and examine NMT and the proteins it modifies. They used living human cancer cells in a large scale study to identify more than 100 proteins that NMT modifies. Most of these proteins were identified for the very first time in their natural environment. The researchers also found several new proteins that NMT could modify during cell apoptosis, a process that is essential in cancer chemotherapy, but often deactivated in drug resistant cancers.
The team then proceeded to map all of the proteins and established that a small drug-like molecule can inhibit NMT’s ability to modify each of these proteins, pointing the way for a potential new treatment for cancer.
"This 'global map' allows us to understand what the effects of inhibiting NMT will be. This means we can determine which diseases it might be possible to combat by targeting NMT, enabling us as a next step to explore how effective such treatments could be," added Professor Tate.
Commenting on the future research direction, Professor Tate said, "On the back of these results we are looking to test a drug that will have the most potent impact on blocking NMT's ability to modify proteins, and we have started working with collaborators at the Institute of Cancer Research and elsewhere on some very promising therapeutic areas. We are still at an early stage in our research but we have already identified several very potent drug-like NMT inhibitors that are active in animal disease models, and we hope to move towards clinical trials over the next five to ten years."
The study is published in the journal Nature Communications.