CETSA - technology to measure the extent to which drugs reach their targets in the cell.

Most drugs work by binding to the target receptor site on the surface of cells or enzymes (which regulate the rate of chemical reactions) within cells, they can either block the physiological function of the protein, or mimics it's effect. Till date drugs are designed by following this phenomenon. Optimization of target engagement by drugs in cells is often challenging, because drug binding cannot be monitored inside cells.

Researchers at Karolinska Institute in Sweden have developed the first method for directly measuring the extent to which drugs reach their targets in the cell - Cellular thermal shift assay (CETSA). 

It is based on the biophysical principle (target proteins usually get stabilized when drug molecules bind). Using this assay, researchers validated drug binding for a set of important clinical targets and monitored processes of drug transport and activation, off-target effects and drug resistance in cancer cell lines, as well as drug distribution in tissues. 

The lack of methods to directly measure the binding of a drug to its target protein has caused a degree of uncertainty in many phases of drug development. In some cases, where drug candidates have not lived up to expectations in clinical trials on humans, it has transpired that the drug molecules have failed to bind to the right protein

The group behind the study believes that CETSA will be an important control stage and a complement to other methods. The team believes that by virtue of its ability to determine whether existing drugs are suitable for individual patients, the method is of potential value to the practice of individualized treatment.

The study was published in the journal Science. 

"We believe that the method can provide an important diagnostic tool in the treatment of cancer, for example, as CETSA can, in principle, enable us to determine which drug is most effective at targeting the proteins in the tumour," says Daniel Martinez, who leads a team in the project.

Image: - http://images.sciencedaily.com/2013/07/130705101541-large.jpg