Novel bivalent ligands carrying potential antinociceptive effects by targeting putative mu opioid receptor and chemokine receptor CXCR4 heterodimers.

ABSTRACT: 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

SUBMITTER: Ma H 

PROVIDER: S-EPMC9187593 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature