Upfront

Pain relief

Researchers have identified a novel compound that, in mice, provides the same painkilling power as the most potent prescription opioids without suppressing respiration — and thus without causing overdoses. It may also be less addictive than opioids.

“This promising drug candidate was identified through an intensively cross-disciplinary, cross-continental combination of computer-based drug screening, medicinal chemistry, intuition and extensive preclinical testing,” says Brian Kobilka, MD, a Stanford professor of molecular and cellular physiology. Kobilka is a senior author of the article describing the work in the Sept. 8, 2016, issue of Nature.

When an opioid such as morphine binds to the mu opioid receptor, a cell-surface protein found throughout the brain and spinal cord, it triggers both pain relief and respiratory suppression. The trick was to find a drug that triggers only the pain relief — and that doesn’t bind to any additional opioid receptors.

The researchers analyzed the mu opioid receptor’s binding pocket, then computationally screened a database of 3 million compounds. After simulations and testing, just one candidate emerged. With a chemical tweak, it fit the receptor like a hand in a glove.

The study, driven by Stanford Distinguished Fellow Aashish Manglik, MD, PhD,  was a collaboration with scientists at Stanford, the University of California-San Francisco, the University of North Carolina and the Friedrich Alexander University in Erlangen, Germany.

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