In order for drugs to have their effects in human cells, they sometimes have to rely on very specific transporter proteins (SLCs). A Vienna research team has now shown that this applies to an astonishingly high number of cytotoxic substances that are used in cancer therapy, for example. The study appeared in the journal “Nature Chemical Biology”.
<! – —
Doubt that most drugs diffuse through the cell membrane
–
The team led by first author Enrico Girardi and Giulio Superti-Furga from the Research Center for Molecular Medicine (CeMM) of the Austrian Academy of Sciences (ÖAW) in Vienna has carried out a comprehensive analysis to determine to what extent SLCs have an influence on whether drugs find their way into cells . CeMM director Superti-Furga showed that there are such cases a few years ago using the active ingredient YM155, which has been tested as a possible cancer drug. At that time it became clear that this substance could only develop its effect if the transporter protein SLC35F2 helped it to get into the cells.
As a result, the scientists created a genetic library of 394 SLCs and analyzed whether some of them have an impact on the activity of 60 drugs, which are used for the treatment of leukemia or other types of cancer and are largely clinically tested, according to one CeMM broadcast. It was shown that around 80 percent of these substances depend on at least one of the SLCs tested. In total, the Viennese researchers were able to identify hundreds of new connections between drugs and transporter proteins.
The investigation now raises “strong doubts that the generally accepted notion that most drugs simply diffuse through the cell membrane to penetrate the cells is correct,” said Superti-Furga. The new study “underlines the increasingly recognized need for a systematic study of the biological functions of SLCs”. According to the scientists, the findings could help to identify resistance and develop targeted therapies in the future.
Service: https://dx.doi.org/10.1038/s41589-020-0483-3
(APA / red, photo: APA / APA (dpa))
–
