Researchers at Karolinska Institutet have developed a novel method to reliably identify which proteins are affected by a certain drug. ProTargetMiner, their proteome signature library of anticancer molecules, is now publicly available.
The researchers developed ProTargetMiner by experimenting on lung cancer cells treated with 56 different kinds of drug. For each of the drugs they first worked out the LC50 concentration and then used this dose for all the drugs. Once half of the cells had died, they examined each cell's proteome to ascertain which proteins the drugs targeted. In further experiments, they tested the drugs on other cells from breast and intestinal tumors, and drew conclusions about the extent to which the drugs are specific or general in their targeting of cancer cells.
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The results of these experiments are described in the searchable database that the researchers have now created, while the method itself is detailed in an article published today in Nature Communications. The idea is for other researchers to be able to perform similar experiments with other drugs using the same model, and to thus expand the database with more target proteins for more substances.
"We find that the cells are killed in different ways by different drugs," says senior author Roman Zubarev. "Not so long ago we used to think that cells could only die in three ways—necrosis, apoptosis or autophagy—but now we've observed at least thirteen different ways in which cells can die. This method can help to speed up certain parts of the process of new drug development or improve our understanding of existing drugs."