Targeting STAT5, a protein linked to leukaemia and other cancer, with a protein degrader has promise.
The protein STAT5 has attracted the attention of researchers for many years as a potential cancer treatment target. STAT5 was subsequently regarded as “undruggable,” despite intensive efforts. But, the University of Michigan Rogel Cancer Center’s researchers have now had success using a fresh strategy.
By using a cellular garbage disposal mechanism, the researchers were able to remove STAT5 from mice and cell cultures. Setting the stage for its potential as a cancer treatment.
Certain blood malignancies grow and progress in a manner largely dependent on STAT5. Yet, attempts to find a small molecule inhibitor to shut down STAT5 have proved fruitless. Prior research has found it difficult to create drugs that bind to STAT5 with a high degree of affinity, a metric of how well they fit together. Even if a substance might bind to the protein, cells and tissue might not absorb it. Finding a substance that inhibits STAT5 alone without impacting any of the other STAT proteins is similarly challenging.
The University of Michigan’s Shaomeng Wang, Ph.D., professor of medicine, pharmacology, and medicinal chemistry, had another thought. He is the Warner-Lambert/Parke-Davis Professor in Medicine.
His laboratory has been developing a new strategy for medication development that targets protein degradation. This is a process that occurs spontaneously in cells to get rid of extra proteins. It’s like the waste disposal, if you will. This mechanism eliminates the undesirable or damaged protein from the cell when it is no longer required to maintain the health of the body.
Unlike a small molecule inhibitor, which is often created to connect with the protein and impair its activity, the protein degrader functions by removing STAT5 proteins from tumour cells and tissues. We’ve solved some of the major problems that were obstacles for scientists trying to target STAT5, according to Wang. “Over the past 20 years, researchers have worked in this area, but no small compounds targeting STAT5 have entered clinical development.
This study demonstrates that STAT5 can be specifically targeted using a protein degradation strategy. Developing a potential therapeutic molecule that targets STAT5 for the treatment of tumours in which this protein plays a significant role is a novel and promising avenue.
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