Small Molecule Compound Developed That Can Degrade the Cancer Promoting Protein SUMO1

Medical Xpress ^ | OCTOBER 14, 2021 | Bob Yirka

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A team of researchers working at the Indiana University School of Medicine, has developed a compound that can degrade the cancer-promoting protein SUMO1. In their paper published in the journal Science Translational Medicine, the group describes their work in attempting to find a degrader for what has been described as an undruggable cancer-related protein.

Prior research has shown that there are some proteins that change cancer proteins in ways that help it form and spread, but which are considered to be undruggable, meaning that it appears unlikely that a drug could be developed that would prevent it from doing its job. Such proteins are considered to be chemically challenging. SUMO1 is one such protein. In 2014 it was found to drive the cell cycle for certain cancers by promoting tumor growth. It does so by attaching to other cancer-forming proteins, and it was the focus of the work by the team in Indiana.

To find a drug that might degrade SUMO1, the researchers screened a drug library of data regarding 1,596 compounds related to protein degradation. They found a molecule called CPD1 that appeared to be a likely candidate for study. After learning more about its characteristics, the researchers developed a new protein called HB007. The researchers tested the new protein under real-world conditions. In mouse models, they found administration of the protein suppressed the development of breast, lung and colon tumors. Further testing also showed that the protein increased survival rates in mouse models compared to control groups. The findings highlight the importance of proteins like SUMO1 in promoting tumor growth, and why more research is required to find ways to counteract them.

The researchers suggest that their work could lead to new ways to fight cancer in humans—two of them have co-founded a startup with that goal in mind. They also suggest that their work could be used as a template for other scientists seeking ways of dealing with 'undruggable' protein degraders.

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Seeking a unique treatment for lobular breast cancer More information: Anita C. Bellail et al, Ubiquitination and degradation of SUMO1 by small-molecule degraders extends survival of mice with patient-derived tumors, Science Translational Medicine (2021). DOI: 10.1126/scitranslmed.abh1486

Journal information: Science Translational Medicine