New tool could be applied during drug development and in the clinic


Researcher at IGP have developed a new tool that enables the visualisation where drugs bind to human proteins. The highly sensitive technique can be used in searches for compounds with specificity for particular target proteins. It could be used in drug discovery processes or to establish the suitability of a given drug regime before therapy selection.

Drugs are designed to bind their target proteins in physiologically relevant tissues and organs to modulate biological functions and elicit desirable clinical outcomes. Information about target engagement at cellular and subcellular resolution is therefore critical for guiding compound optimisation in drug discovery. It is also important for probing resistance mechanisms to targeted therapies in clinical samples.

Despite significant methodological advances in the assessment of such target engagement among cells and tissues, preclinical testing often fails to fully capture human responses to drugs. This can lead to attrition in clinical trials because of insufficient efficacy or compromised safety.

“The new tool that we have developed is called target engagement-mediated amplification (TEMA) technology. It has the potential to aid in drug development and clinical routine by conferring valuable insights in drug-target interactions at spatial resolution in protein arrays, cells and in tissues,” says Rasel Al-Amin, first author of the paper that describes the new technique.

In the TEMA technology the physical interaction between a drug substance and a target molecule is identified by oligonucleotide probes, which are subsequently amplified by a process called rolling circle amplification. When enough amplification products have been produced, they can be visualised by fluorophores that emit light. This permits the detection of both the proteins that interact and where it happens.

“Our study shows that TEMA represents a new promising approach to demonstrate target engagement by drugs in relevant biological material. This makes it suitable for application in the drug discovery process or for analysing for instance tumour samples to predict patient responses to drugs,” says Rasel Al-Amin.

The study is a collaboration with researchers at the Chemical Biology Consortium Sweden, SciLifeLab, the Departments of Medical Sciences, Pharmacy and Chemistry BMC at Uppsala University, Karolinska Institute, Medical University of Innsbruck, Austria. It has been published in the journal Nucleic Acids Research

More information:
Paper in Nucleic Acids Research
Rasel Al-Amin’s research in Ulf Landegren’s group

Last modified: 2022-01-26