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Drug research: New technique shows if drugs have reached intended target

Date:
July 18, 2013
Source:
Nanyang Technological University
Summary:
The search for new drugs, including those for cancer, is set to speed up thanks to a new research technique which could tell if drugs had reached their intended target.

(Left) Principal investigator Prof Par Nordlund and Senior Research Fellow Dr Andreas Larsson, with imaging results from their newly invented Cellular Thermal Shift Assay (CETSA) method.
Credit: Image courtesy of Nanyang Technological University

The search for new drugs, including those for cancer, is set to speed up thanks to a new research technique invented by scientists at the Nanyang Technological University (NTU).

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Named the "Cellular Thermal Shift Assay" (CETSA), scientists can now know for sure if a drug had reached its target protein in the body, which is a critical step in determining the effectiveness of most medicines.

Presently, scientists can only hypothesise if a drug has indeed reached its target protein, leading to expensive and prolonged drug development process. CETSA will help scientists take out much of the usual trial-and-error guesswork from the drug development equation.

This research breakthrough was recently published in Science.

Most drugs operate by binding to one or more proteins, which 'blocks' the proteins' function. Scientists around the world face two common bottlenecks: how to identify the right proteins to target and how to design drug molecules which are able to efficiently seek out and bind to these proteins.

CETSA's inventor, Professor Pär Nordlund from NTU's School of Biological Sciences, said their new method will not only ease the two bottlenecks, but also has important applications in monitoring a patient's progress, for example, during cancer treatment.

"With CETSA, we can in principle determine which drug and treatment regime is most effective at targeting the proteins in the tumour in cancer patients, and monitor when resistance is developing," says Prof Nordlund.

How CETSA works

When drugs react with target proteins in a cell, the proteins are able to withstand higher temperature before unfolding and precipitating, that is, turning solid. An example of protein precipitation is when liquid egg white (which is protein) is cooked (turning solid) at high heat.

"By heating protein samples and finding out which proteins are 'cooked' and which are left 'uncooked' due it being more heat resistant, we are able to know if the drugs had reached their target cells and if it had caused the desired binding to the proteins, blocking its functions," added Prof Nordlund, who is also a Professor of Biophysics at the Karolinska Institutet.

"With CETSA, costly and challenging drug development cycles can potentially be made more efficient, as the method can be used as a stringent control step at many phases of the process. Other methods are available for indirect measurements of drug binding but they are often less accurate, and CETSA will be a valuable tool to complement these technologies," said the Swedish professor.

This project took Prof Nordlund's team three years and they are now in the process of developing a prototype device.


Story Source:

The above story is based on materials provided by Nanyang Technological University. Note: Materials may be edited for content and length.


Journal Reference:

  1. D. M. Molina, R. Jafari, M. Ignatushchenko, T. Seki, E. A. Larsson, C. Dan, L. Sreekumar, Y. Cao, P. Nordlund. Monitoring Drug Target Engagement in Cells and Tissues Using the Cellular Thermal Shift Assay. Science, 2013; 341 (6141): 84 DOI: 10.1126/science.1233606

Cite This Page:

Nanyang Technological University. "Drug research: New technique shows if drugs have reached intended target." ScienceDaily. ScienceDaily, 18 July 2013. <www.sciencedaily.com/releases/2013/07/130718101407.htm>.
Nanyang Technological University. (2013, July 18). Drug research: New technique shows if drugs have reached intended target. ScienceDaily. Retrieved October 25, 2014 from www.sciencedaily.com/releases/2013/07/130718101407.htm
Nanyang Technological University. "Drug research: New technique shows if drugs have reached intended target." ScienceDaily. www.sciencedaily.com/releases/2013/07/130718101407.htm (accessed October 25, 2014).

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