PLK1, a cancer drug target?
without the side effects commonly associated with existing cancer
drugs, has been discovered by scientists who believe this target is
linked to other diseases including diabetes and Alzheimers.
The drug target, a key regulatory enzyme called protein kinase, catalyses the processes that regulate a protein's functional activities. Defects in specific protein kinases have been linked to over 400 diseases and about 25 per cent of pharmaceutical research and development is now focused on the discovery and evaluation of protein kinase inhibitors for therapeutic applications.
In additon, the research also resulted in the development of a proprietary assay to screen for PLK1 inhibitory compounds that could serve as cancer drug candidates.
Scientists at the University of British Columbia, in partnership with proteomics company Kinexus, discovered a novel phosphorylation site on the abundant nuclear protein B23. This phosphorylation event was shown to be an essential step during the cell's replication process.
The Polo-like kinase-1 (PLK1) was the principal protein kinase that carried out B23 phosphorylation at this site. Inhibition of PLK1 is predicted to block the reproduction of cancer cells indicating its potential as a promising cancer drug target.
Dr. Steven Pelech, president of Kinexus told DrugResearcher.com that along with the PLK1, Kinexus had already identified the JNK and p38 MAPK protein kinases as drug targets using the Kinetworks method.
The Kinetworks is a screening solution identifying relevant proteins in different model systems and disease states. It is designed to diminish risk while maximizing prospects in discovery-based research. The application of these methods in characterising cell-signalling networks provides knowledge for drug development, rational drug design, disease diagnosis, and ultimately personalized therapies.
Pelech explained: "We offer unique antibody-based proteomics services to track the expression and phosphorylation states of hundreds of protein kinases and other key cell signalling proteins in cells and tissues from hundreds of diverse patients samples and experimental animal model systems."
"We plan to harvest this data to identify disease markers and therapeutic drug targets. Using our proteomics capabilities, we intend to commence high throughput drug screen against several of the kinase drug targets within the next two years."
According to Pelech, the kinetworks represents a new standard that surpasses previous analytical protein tools such as 2D gels and mass spectrometry. These techniques have proved to be "very inadequate" for tracking signal transduction proteins that are upto 1000 times lower in concentration than structural proteins and metabolic pathway enzymes.
"The use of antibodies has become the industry standard to accurate and sensitive detection and quantitation of proteins," he added.
The latest research findings are published in the September printed issue of the Journal of Biological Chemistry and are currently available on JBC Online.
