Researchers find new approach to drug development

Zurich – Researchers at the University of Zurich have determined the three-dimensional structure of the receptor that causes nausea during chemotherapy. Their finding contributes to the development of drugs both for these side effects and to treat other conditions.

Nausea and vomiting during chemotherapy is caused by a receptor in the brain, writes the University of Zurich in a statement. The receptor is normally activated by the neurokin 1 receptor, which is greatly overstimulated during the cancer treatment.

For years, scientists have been looking for effective inhibitors – but have had only limited success. Researchers at the University of Zurich have now managed to show what the three-dimensional structure of the receptor looks like when drugs are used.

They found that the actives in effective drugs altered some parts of the receptor to the extent that the drugs could not easily escape. Conversely, the actives in less effective drugs were able to fit just as well onto the receptor but could still quickly leave it.

The study also helped determine which chemical structures of the drugs enable a long-lasting attachment to the receptor and thus a durable effect. “This result provides important insights on how to make such highly potent compounds in the future,” commented researcher Andreas Plückthun.

The new research could also help develop effective treatments for the many other disorders that are influenced by this receptor – among them migraine, asthma, incontinence, inflammation and depression. Furthermore, it may be useful in the search for compounds that could be effective on other receptors, thanks to the important clues it gives about the general features that define a long-acting clinically successful drug.

“We could only find this out because we could directly see the structure in such high detail, and this in turn only became possible through the directed evolution and protein engineering methods we have developed over the last few years,” concluded Plückthun.

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