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11/02/2024 07:30:06 am

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New Discovery Could Improve Future Chemotherapies

Cancer drugs

(Photo : Wikimedia commons) Six bottles of cancer drugs

Scientists have found a new mechanism to suppress proteasomes, structures of protein that are targeted in cancer therapies.

The results of the study could possibly lead to a new generation of chemotherapy medicines much more effective at honing in on offending cells than existing drugs, and be far less toxic, said a study from the Brazilian Center for Research in Energy and Materials' Brazilian Biosciences National Laboratory.

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"We have already developed a series of molecules based on the newly identified mechanism," said researcher Daniela Trivella.

"Now we plan to synthesize them in partnership with CNPEM researcher Marjorie Bruder and test their potential. The goal is to optimize the proteasome inhibition effect, make the compound even more selective of tumor cells and eliminate the resistance problems found with drugs that are currently available on the market."

The proteasome, which belongs to a category of enzymes called proteases, is a protein compound that governs numerous core functions in cells.

The functions include managing the cell division process, proliferation and apoptosis (or programmed cell death), as well as eradicating non-functioning or harmful proteins.

Carfilzomib, a drug based on the natural molecule epoxomicin, was approved in 2012.

In the same year, researchers from the United States and Brazil were able to isolate a similar molecule called epozyketone from carmaphycin, a species of cyanobacterium  found in the Caribbean.

The reactive group (the part of the molecule able to interact with the proteasome) of both compounds are the same.

"Epoxyketones are very potent selective inhibitors of the proteasome because they interact with this enzyme in two stages: the first reversible and the second irreversible," Trivella explained.

Scienteists from the Scripps Institution of Oceanography at the University of California in San Diego created artificial analogs of the compounds with small modifications in the structure, to optimize their effect and try to find additional reactive groups.

With the newly developed substances' proteaseome inhibition, the team plans to synthesize and test other possibilities of the compound and determine their impact on therapeutic applications, such as killing malignant tumor cells and leaving healthy ones intact.

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