Researchers develop new chemical probe as promising tool for drug discovery and therapeutics
By Cam Buchan
Development of a new potent chemical probe by a global team that includes Schulich Medicine & Dentistry researchers is paving the way for the creation of future innovative treatments for cancer and other neurodevelopmental diseases.
In collaboration with the Structural Genomics Consortium (SGC) in Toronto and other international partners, researchers in the Schild-Poulter Laboratory have focused on a particular protein in the E3 ubiquitin ligases family, called the C-terminal to LisH (CTLH) complex.
The role of CTLH is to tag other proteins for degradation – essentially terminating those proteins it identifies as damaged or no longer needed – through a process called ubiquitination. Deficiencies in this process are linked to numerous diseases, including cancer, Parkinson's disease and several immune and neurodevelopmental disorders.
The ubiquitin ligase complex has attracted much attention recently because of its involvement in a wide variety of cellular regulations and its potential use in a technique called Targeted Protein Degradation (TPD). TPD uses small molecules to selectively degrade harmful proteins, harnessing the natural ability of E3 ubiquitin ligases to tag proteins for destruction.
But its exact function and the proteins it targets in humans have remained a mystery, said Caroline Schild-Poulter, PhD, a scientist in the Molecular Medicine Research Group at Robarts Research Institute.
Now research, recently published in Nature Chemical Biology by Schild-Poulter and her team, is revealing its secrets.
Using a powerful new technique that captures interactions occurring inside cells, Schild-Poulter and team have validated the specificity and potency of the new compound created by Pfizer called PFI-7.
This means that PFI-7 can now be used as an effective tool to study the CTLH complex's role in cells and explore new disease treatment strategies.
“Understanding the properties of CTLH enhances our ability to study the intricate mechanisms of protein degradation and opens up new avenues for innovative treatments for cancer and other diseases,” said Schild-Poulter. “This collaboration also demonstrates the benefit of shared knowledge and resources in driving scientific discovery and improving human health."
Work in the Schild-Poulter Laboratory globally aims at understanding the mechanisms governing the maintenance of genomic stability and uncovering the causes of cell transformation and cancer development.
Her team plans further investigation into the functions of the CTLH complex in cancer development and neurodevelopmental diseases.
