Toward the development of bivalent ligand probes of cannabinoid CB1 and orexin OX1 receptor heterodimers

Brian F. Thomas; Yanan Zhang; Brian P. Gilmour; DA Perrey; Brian P. Gilmour; Brian F. Thomas; Yanan Zhang

Toward the development of bivalent ligand probes of cannabinoid CB1 and orexin OX1 receptor heterodimers

Perrey, DA., Gilmour, B., Thomas, B., & Zhang, Y. (2014). Toward the development of bivalent ligand probes of cannabinoid CB1 and orexin OX1 receptor heterodimers. ACS Medicinal Chemistry Letters, 5(6), 634-638. https://doi.org/10.1021/ml4004759

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Abstract

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.