Combination of technologies could be used in drug development


A new combination of technologies can be used to examine how drugs interact with their targets. This is shown by IGP researchers in a paper published in the journal Analytical Chemistry. The method can be used to analyse a large number of samples, in particular for small sample sizes, and could be applied during drug development and in the clinic.

The efficacy of drugs depends on how well the compounds can modulate the primary target molecule; a process referred to as target engagement. Similarily, interactions with unintended target proteins can result in toxicity and other adverse effects.

The ability to monitor target engagement in cellular contexts is therefore important during the development of new drugs. In the present study the researchers have studied a new method to do so.

“In the early hit identification phase of drug development an assay called CETSA can be combined with mass spectrometry to reveal drug-target engagement for large sets of proteins. However, the analysis is slow, requires substantial amounts of the sample material and it often misses proteins of specific interest. We have instead combined CETSA with the PEA technique, a variant of proximity assays previously developed in our lab, and found that it worked equally well,” says Rasel Al-Amin, researcher in Ulf Landegren’s group and first author of the paper.

The new combination of methodologies allows analyses of target engagement with large numbers of proteins. This renders the technique suitable when many drug candidates or many samples should be analysed. The approach will be particularly valuable when limited amounts of materials are available. It could potentially also be used for corresponding analyses in routine clinical care.

More information:
Paper in Analytical Chemistry
Rasel Al-Amin’s research in Ulf Landegren’s group