Novel bivalent ligands carrying potential antinociceptive effects by targeting putative mu opioid receptor and chemokine receptor CXCR4 heterodimers.
Bivalent ligand
Chemokine receptor CXCR4
Mu opioid receptor
Pain management
Journal
Bioorganic chemistry
ISSN: 1090-2120
Titre abrégé: Bioorg Chem
Pays: United States
ID NLM: 1303703
Informations de publication
Date de publication:
03 2022
03 2022
Historique:
received:
01
10
2021
revised:
12
01
2022
accepted:
21
01
2022
pubmed:
31
1
2022
medline:
14
6
2022
entrez:
30
1
2022
Statut:
ppublish
Résumé
The functional interactions between opioid and chemokine receptors have been implicated in the pathological process of chronic pain. Mounting studies have indicated the possibility that a MOR-CXCR4 heterodimer may be involved in nociception and related pharmacologic effects. Herein we have synthesized a series of bivalent ligands containing both MOR agonist and CXCR4 antagonist pharmacophores with an aim to investigate the functional interactions between these two receptors. In vitro studies demonstrated reasonable recognition of designed ligands at both respective receptors. Further antinociceptive testing in mice revealed compound 1a to be the most promising member of this series. Additional molecular modeling studies corroborated the findings observed. Taken together, we identified the first bivalent ligand 1a showing promising antinociceptive effect by targeting putative MOR-CXCR4 heterodimers, which may serve as a novel chemical probe to further develop more potent bivalent ligands with potential application in analgesic therapies for chronic pain management.
Identifiants
pubmed: 35093692
pii: S0045-2068(22)00046-3
doi: 10.1016/j.bioorg.2022.105641
pmc: PMC9187593
mid: NIHMS1777909
pii:
doi:
Substances chimiques
Analgesics
0
Ligands
0
Receptors, Opioid, mu
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
105641Subventions
Organisme : NIDA NIH HHS
ID : P30 DA033934
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA033930
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA044855
Pays : United States
Informations de copyright
Copyright © 2022 Elsevier Inc. All rights reserved.
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