TY - JOUR
T1 - Molecular basis of opioid receptor signaling
AU - Che, Tao
AU - Roth, Bryan L.
N1 - Publisher Copyright:
© 2023 Elsevier Inc.
PY - 2023/11/22
Y1 - 2023/11/22
N2 - Opioids are used for pain management despite the side effects that contribute to the opioid crisis. The pursuit of non-addictive opioid analgesics remains unattained due to the unresolved intricacies of opioid actions, receptor signaling cascades, and neuronal plasticity. Advancements in structural, molecular, and computational tools illuminate the dynamic interplay between opioids and opioid receptors, as well as the molecular determinants of signaling pathways, which are potentially interlinked with pharmacological responses. Here, we review the molecular basis of opioid receptor signaling with a focus on the structures of opioid receptors bound to endogenous peptides or pharmacological agents. These insights unveil specific interactions that dictate ligand selectivity and likely their distinctive pharmacological profiles. Biochemical analysis further unveils molecular features governing opioid receptor signaling. Simultaneously, the synergy between computational biology and medicinal chemistry continues to expedite the discovery of novel chemotypes with the promise of yielding more efficacious and safer opioid compounds.
AB - Opioids are used for pain management despite the side effects that contribute to the opioid crisis. The pursuit of non-addictive opioid analgesics remains unattained due to the unresolved intricacies of opioid actions, receptor signaling cascades, and neuronal plasticity. Advancements in structural, molecular, and computational tools illuminate the dynamic interplay between opioids and opioid receptors, as well as the molecular determinants of signaling pathways, which are potentially interlinked with pharmacological responses. Here, we review the molecular basis of opioid receptor signaling with a focus on the structures of opioid receptors bound to endogenous peptides or pharmacological agents. These insights unveil specific interactions that dictate ligand selectivity and likely their distinctive pharmacological profiles. Biochemical analysis further unveils molecular features governing opioid receptor signaling. Simultaneously, the synergy between computational biology and medicinal chemistry continues to expedite the discovery of novel chemotypes with the promise of yielding more efficacious and safer opioid compounds.
UR - http://www.scopus.com/inward/record.url?scp=85177787686&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2023.10.029
DO - 10.1016/j.cell.2023.10.029
M3 - Review article
C2 - 37995655
AN - SCOPUS:85177787686
SN - 0092-8674
VL - 186
SP - 5203
EP - 5219
JO - Cell
JF - Cell
IS - 24
ER -