Scientists at the Nanyang Technological University Developed innovative technique that can tell if drugs have hit their target in the human body. (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).
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
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, one of the world’s top scientific journals.
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
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
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
“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, one of Europe's most prestigious medical
universities, located in Sweden.
“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. They are also in talks
with pharmaceutical companies who are interested to collaborate in
Prof Nordlund is a leading structural biologist instrumental in
establishing the laboratory of the Structural Genomics Consortium at
Karolinska Institutet (Stockholm), and had received the prestigious
Göran Gustafsson prize in chemistry from the Swedish Academy of Sciences
He is also a member of the Nobel Assembly at the Karolinska Institutet and the Chemistry Class at the Swedish Academy of Science, as well as a Reviewing Editor at Science Magazine. In addition, he is the co-founder of three biotech companies Evitra Proteoma, Sprint Biosciences and Pelago Bioscience.
Source: Nanyang Technological University