title: A bivalent ligand (KMN-21) antagonist for mu/kappa heterodimeric opioid receptors.
abstract: In an effort to develop antagonists for kappa-mu opioid receptor heterodimers, a series of bivalent ligands 3-6 containing kappa- and mu-antagonist pharmacophores were designed and synthesized. Evaluation of the series in HEK-293 cells revealed 4 (KMN-21) to selectively antagonize the activation of kappa-mu heterodimers, suggesting possible bridging of receptors when the bivalent ligand spacer contains 21 atoms.
authors.affiliation: Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Shijun
authors.initials: S
authors.lastname: Zhang
authors.forename: Ajay
authors.initials: A
authors.lastname: Yekkirala
authors.forename: Ye
authors.initials: Y
authors.lastname: Tang
authors.forename: Philip S
authors.initials: PS
authors.lastname: Portoghese
mesh_terms: D002460:Cell Line; D006146:Guanidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D008024:Ligands; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors*; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors*
chemical_list: D006146:Guanidines; C546970:KMN-21 compound; D008024:Ligands; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D009271:Naltrexone