by In a significant breakthrough, researchers from Mass General Brigham have developed new compounds that show great potential in inhibiting the growth of cancer cells. The compounds specifically target a protein-degrading complex called proteasomes, which are essential for the survival of cancer cells. The study, published in the Proceedings of the National Academy of Sciences, describes the development of compounds that inhibit a specific active site of proteasomes, known as β2.
Proteasome inhibitors are a commonly used treatment for diseases like multiple myeloma and mantle cell lymphoma. However, the current FDA-approved inhibitors primarily target one active site called β5. Despite their effectiveness, these drugs have limitations such as severe side effects and drug resistance. Therefore, the development of inhibitors that target additional active sites, such as β2, is a significant step forward in cancer treatment.
The researchers took a unique approach in identifying these new inhibitors. Instead of screening thousands of compounds, they relied on previous work that identified the structure of PI31, a natural proteasome inhibitor. Building upon this knowledge, they designed small molecules that could specifically inhibit the β2 proteasome site without affecting the other active sites.
The researchers conducted preclinical tests using one of the synthesized compounds, ARFL-Boro, on multiple myeloma cells. The results were promising, as the compound effectively inhibited the growth of these cancer cells both on its own and in combination with an existing β5 inhibitor drug. This suggests that using the newly identified compound in combination with existing drugs could help overcome therapeutic resistance and potentially reduce side effects.
Dr. John Hanna, the corresponding author of the study, emphasized the significance of these findings. “We used this approach to develop a new class of proteasome inhibitors and found that they were strongly active against multiple myeloma,” said Dr. Hanna. He added that the discovery of β2 as a therapeutic target for multiple myeloma opens up exciting opportunities for drug development.
This breakthrough offers hope to cancer patients and healthcare professionals alike. The development of compounds that specifically target different active sites of proteasomes not only expands treatment options but also has the potential to improve outcomes and reduce the adverse effects associated with current drugs.
While further research and clinical trials are needed to validate these findings, this study represents a significant step forward in the field of cancer therapeutics. The researchers’ rational design approach and focus on inhibiting the β2 active site provide a promising foundation for future drug development efforts.
As the fight against cancer continues, breakthroughs like these hold the key to more effective and targeted treatment options. With continued advancements in medical research, we are inching closer to a future where cancer can be controlled, if not eradicated entirely.
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- Source: Coherent Market Insights, Public sources, Desk research
- We have leveraged AI tools to mine information and compile it
