Rising of new generation of chemotherapies

A new mechanism has been found to inhibit proteasomes, protein complexes that are a target for cancer therapy. Researchers say they have already developed a series of molecules based on the newly identified mechanism. They are planning to synthesize them in partnership with CNPEM researcher Marjorie Bruder and test their potential. Their 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. They discovered that a chemical reaction called hydroamination occurs, which had never before seen under physiological conditions. This type of reaction is frequently used by synthetic chemists in preparing substances, but normally it requires very specific temperature and pH conditions and the use of catalysts to occur. It has never been reported as a mechanism of enzyme inhibition. Inspired by this new mechanism for proteasome inhibition, the LNBio group plans to synthesize and test a new series of carmaphycin-syringolin enone analogs to determine their effects on the therapeutic window (preferential death of tumor cells in relation to healthy cells) and assess whether they are also capable of reacting with proteasomes that are resistant to traditional inhibitors.