A protein degrader shows potential in targeting STAT5, a protein involved in leukemia and other forms of cancer. For decades, researchers have been interested in targeting the protein STAT5 in the fight against cancer. However, despite extensive efforts, STAT5 was eventually considered 'undruggable
Graphical representation of the protein degrader attacking STAT5 Credit: Wang Lab/Michigan Medicine
STAT5 plays a key role in how some blood cancers develop and progress. But efforts to identify a small molecule inhibitor to block STAT5 have been stymied. Previous research efforts have found it challenging to design a drug to bind to STAT5 with a high-affinity, a measure of how well they fit together. Even when a compound was found to bind with the protein, it may not make its way into cells and tissue.
Using this approach, Wang’s lab identified a protein degrader, AK-2292, that targets and removes STAT5. The compound was highly specific to STAT5 with no effect on other STAT proteins. It was effectively taken up by both cell lines and mouse models and was found to stop cell growth in cell lines of human chronic myeloid leukemia and to induce tumor regression in mouse models of CML.
Wang’s lab has been investigating protein degraders for several years and has a number of degraders in advanced preclinical development studies, which they hope will lead to clinical trials for the treatment of cancer in people.
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