Are We One Step Closer to a New Molecule?

New Research Suggests Selective Activation of Kappa Opioid Receptor May Be Possible

Researchers at the University of North Carolina School of Medicine, supported by collaborating scientists from other institutions, have reported major new insights that may illuminate the route to opioids that relieve pain without provoking the adverse effects that underlie the current opioid epidemic. The advance involves solving the crystal structure of the activated kappa opioid receptor (KOR) bound to a morphine derivative, using a unique technique called Lipidic Cubic Phase crystallization. Senior author Bryan Roth, MD, PhD, noted “To create better opioids, we need to know the structure of their receptors. Until recently, this was impossible. But now we know the structure of the activated kappa opioid receptor. And we showed we can actually use the structure to make a drug-like compound with better properties than current opioids.” The findings appear in the journal Cell.

Of the adverse effects of current opioid therapy, Dr. Roth commented “Tens of thousands people who take opioids die every year, and so we need safer and more effective drugs for treating pain and related conditions. One of the big ideas is to target KORs because the few drugs that bind to it don’t lead to addiction or cause death due to overdose. Those side effects are mainly related to actions at the mu opioid receptor.” With a new understanding of its crystal structure, the research team was able to identify the parts of the KOR were key to the binding of drug-like compounds, and then to synthetize a new compound that proved extremely selective for KORs only. First author Tao Che, PhD, commented “It’s now possible to design new drugs based on the findings on this active KOR structure and tweak them to only have the desired pain relief effects.”

Read about the discovery.

The journal abstract may be read here.


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