CeMM Research Center and Collaborators Uncover Hidden Mechanism of 70-Year-Old Leukemia Drug
A team of scientists from the CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, in collaboration with researchers from the University of Oxford, the Weizmann Institute of Science, and the University of Dundee, has uncovered a previously unknown mechanism by which the 70-year-old leukemia drug 6-thioguanine (6-TG) affects cells. For decades, the drug's effects were well-documented, but the molecular details of why some cells are killed while others resist remained unclear. The new research identifies a protein called NUDT5 as an unexpected factor in this response. Crucially, the study found that NUDT5 influences 6-TG sensitivity not through its enzymatic activity, as initially expected, but through its physical presence as a molecular scaffold that organizes cellular metabolism. By using targeted protein degradation to remove NUDT5, researchers observed that cells became protected from the drug's toxic effects, a finding missed by traditional enzyme inhibitors.
