In experiments on mice, tumor growth decreased by 42%
The press service of the Higher School of Economics (HSE) reported that scientists from the university’s Laboratory of Bio- and Chemoinformatics—working with colleagues from Jinan University in China and the St. Petersburg State Institute of Technology—have developed molecules capable of destroying the GPX4 protein. This protein protects cancer cells from oxidative stress. The compounds contain an azide group consisting of three nitrogen atoms and utilize a mechanism of targeted proteolysis.
According to Maxim Gureev, a senior researcher at the HSE Laboratory of Bio- and Chemoinformatics, the molecules bind simultaneously to GPX4 and the enzyme UHRF1. Subsequently, E3 ubiquitin ligase tags the protein with ubiquitin, and the cell’s proteasomes break it down. The efficiency of GPX4 removal reached 84%.
Destroying the protein triggered ferroptosis: glutathione levels in the cells dropped, while lipid oxidation and iron content increased.
Gureev noted that in experiments involving mice with transplanted tumors, a ten-day course of the compounds slowed tumor growth by nearly 42% without causing significant weight loss in the animals. The researchers plan to further improve the efficacy of the developed molecules.
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