Open AccessToward the Development of Bivalent Ligand Probes of Cannabinoid CB1 and Orexin OX1 Receptor Heterodimers
Author(s) -
David A. Perrey,
Brian P. Gilmour,
Brian F. Thomas,
Yanan Zhang
Publication year - 2014
Publication title -
acs medicinal chemistry letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.065
H-Index - 66
ISSN - 1948-5875
DOI - 10.1021/ml4004759
Subject(s) - cannabinoid receptor , bivalent (engine) , pharmacophore , receptor , orexin , cannabinoid , chemistry , endocannabinoid system , in vitro , microbiology and biotechnology , biochemistry , biology , neuropeptide , antagonist , metal , organic chemistry
Cannabinoid CB1 and orexin OX1 receptors have been suggested to form heterodimers and oligomers. Aimed at studying these complexes, a series of bivalent CB1 and OX1 ligands combining SR141716 and ACT-078573 pharmacophores were designed, synthesized, and tested for activity against CB1 and OX1 individually and in cell lines that coexpress both receptors. Compound 20 showed a robust enhancement in potency at both receptors when coexpressed as compared to individually expressed, suggesting possible interaction with CB1-OX1 dimers. Bivalent ligands targeting CB1-OX1 receptor dimers could be potentially useful as a tool for further exploring the roles of such heterodimers in vitro and in vivo.