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Papers of the Week

Papers: 3 Apr 2021 - 9 Apr 2021

Pharmacology/Drug Development

2021 Apr 06

Sci Signal



Editor's Pick

Biased ligands at opioid receptors: Current status and future directions.


Che T, Dwivedi-Agnihotri H, Shukla AK, Roth BL
Sci Signal. 2021 Apr 06; 14(677).
PMID: 33824179.


The opioid crisis represents a major worldwide public health crisis that has accelerated the search for safer and more effective opioids. Over the past few years, the identification of biased opioid ligands capable of eliciting selective functional responses has provided an alternative avenue to develop novel therapeutics without the side effects of current opioid medications. However, whether biased agonism or other pharmacological properties, such as partial agonism (or low efficacy), account for the therapeutic benefits remains questionable. Here, we provide a summary of the current status of biased opioid ligands that target the μ- and κ-opioid receptors and highlight advances in preclinical and clinical trials of some of these ligands. We also discuss an example of structure-based biased ligand discovery at the μ-opioid receptor, an approach that could revolutionize drug discovery at opioid and other receptors. Last, we briefly discuss caveats and future directions for this important area of research.