Researchers have reported progress in cancer treatment using glutarimide-based molecules that can interfere with a cellular system responsible for protein disposal, showing promise against bone marrow cancer with minimal side effects. The findings were announced by the press service of the research federation responsible for the study.
Even with new therapies emerging, cancer remains a major health challenge. A growing area of interest focuses on depriving malignant cells of the proteins they need to grow and replicate. The strategy hinges on guiding these critical proteins into specialized structures called proteasomes, which act as cellular recycling centers. Certain enzymes, collectively known as ubiquitinases, including Cereblon, help tag defective or surplus proteins for destruction. If cancer-related proteins can be marked in this way, the body can naturally remove them. Existing treatments leveraging this approach sometimes rely on compounds that bind Cereblon but carry toxicity that limits their use.
In St. Petersburg and collaborating institutes, scientists explored an alternative route. They designed molecules derived from glutarimide, an organic nitrogen-containing scaffold known to fit the Cereblon binding pocket. The key aim was to create compounds that can mark cancer proteins without provoking harmful effects. Through systematic modification, the team generated a library of 20 distinct complex molecules. These variants differ in small functional groups that influence how the molecules carry a charge and how strongly they interact with Cereblon. Notably, sulfur-containing derivatives showed the strongest affinity, binding Cereblon with roughly double the efficiency of several current analogues.
Subsequent laboratory tests involved exposing cultures of myeloma cells, a form of bone marrow cancer, to the most promising candidates. The results demonstrated a reduction in the cleavage of proteins necessary for cancer cell survival, indicating that these glutarimide-based compounds can effectively engage the protein disposal pathway without triggering significant toxicity. This demonstrates the potential to develop a new class of chimeric inhibitors that could degrade a broader set of disease-related proteins while preserving normal cells. The implications extend beyond myeloma, suggesting a versatile approach for targeting proteins involved in various cancers and other diseases. As researchers emphasize, translating these findings from cell cultures to safe, effective therapies will require rigorous additional studies, including animal models and clinical trials. Still, the work offers a compelling proof of concept that selective Cereblon engagement, guided by glutarimide scaffolds, can yield potent anti-cancer activity with an improved safety profile. [citation needed]
Experts warn that while the data are encouraging, practical application depends on a careful balance between efficacy and safety. The focus now shifts to refining the molecular designs to enhance selectivity for cancerous cells, minimizing off-target effects, and ensuring favorable pharmacokinetics. If successful, this line of research could lead to a new generation of therapies that disable disease-driving proteins by exploiting the body’s own protein-degradation machinery, offering a potential path for broader treatment options in oncology. Ongoing investigations aim to define precisely which cancer-related proteins are most amenable to this approach and how best to deploy these compounds in combination with existing treatments. [citation needed]