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Impact

Mapping the Kappa Opioid Receptor Using RTI's JDTic Compound

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  • Mapping the Kappa Opioid Receptor Using RTI's JDTic Compound

New insights enable structure-based discovery of new drugs

The medicinal value of opioid drugs as painkillers and sedatives is well known, as is their potential for addiction. As researchers seek safer and more effective opioids to treat addiction, depression, and other conditions, one major gap in their ability to identify promising compounds has long been a lack of knowledge of the structure of the kappa opioid receptor (KOR).

To address this need, RTI joined a research team led by the Scripps Research Institute, collaborating with scientists from the University of North Carolina at Chapel Hill and Virginia Commonwealth University to map the structure of this key receptor in the human brain that moderates pleasure, pain, addiction, depression, psychosis, and related conditions.

Using a Synthesized Compound to Determine the 3-D Atomic Structure of the Kappa Opioid Receptor

To determine the structure of KOR, researchers needed a high-resolution image of the compound in its inactive state. To obtain this image, they used a compound called JDTic, which was designed, synthesized, and developed by RTI with support from the National Institute on Drug Abuse (NIDA). In 2005, we donated JDTic to NIDA’s Drug Supply Program to make it available as a research tool.

With our JDTic compound bound to the KOR, the receptor was rendered inactive and could be imaged. The close fit of the points of contact between JDTic and KOR allowed researchers to accurately determine the map of the atomic structure of the kappa opioid receptor in humans.

Enabling the Design of New, Effective Treatments for Addiction, Depression, and Other Conditions

Uncovering the structure of KOR delivers a long-awaited molecular framework for understanding drug action, while enabling structure-based discovery of new drugs with ideal pharmacological properties. The finding also paves the way for research institutions, academia, and drug companies to pursue improvements to existing KOR-targeted compounds.

Using the κ-OR structure, along with other information, scientists may now be able to develop drugs that target the receptor to limit negative side effects of opioid drugs used medicinally, such as morphine and codeine. This understanding could lead to a new generation of therapeutic drugs to treat addiction, chronic pain, anxiety, depression and other conditions.

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  • The Scripps Research Institute

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  • National Institutes of Health

Our Experts

Scott Runyon Director, Organic and Medicinal Chemistry

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Behavioral Health Research

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Medicinal Chemistry Behavioral Pharmacology Molecular Design and Cheminformatics In Vitro Pharmacology, Bioassay Development, and High-Throughput Screening (HTS)

Learn More

Structure of the human kappa opioid receptor in complex with JDTic (Nature, 2012)

The kappa opioid receptor antagonist JDTic attenuates alcohol seeking and withdrawal anxiety (Addiction Biology, 2012)

Effect of the selective kappa-opioid receptor antagonist JDTic on nicotine antinociception, reward, and withdrawal in the mouse (Psychopharmacology, 2010)

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