title: Design and evaluation of a novel fluorescent CB2 ligand as probe for receptor visualization in immune cells.
abstract: Cannabinoid CB2 receptor has emerged as a very promising target over the last decades. We have synthesized and evaluated a new fluorescent probe designated NMP6 based on 6-methoxyisatin scaffold, which exhibited selectivity and K(i) value at hCB2 of 387 nM. We have demonstrated its ability to be an effective probe for visualization of CB2 receptor binding using confocal microscopy and a flow cytometry probe for the analysis of CB2 protein expression. Furthermore, NMP6 was easily obtained in two chemical steps from commercially available building blocks.
authors.affiliation: Core Laboratory for Neuromolecular Production, Department of Biomedical and Pharmaceutical Sciences, University of Montana, Missoula, MT 59812, USA.
authors.forename: Ravil R
authors.initials: RR
authors.lastname: Petrov
authors.forename: Maria E
authors.initials: ME
authors.lastname: Ferrini
authors.forename: Zeina
authors.initials: Z
authors.lastname: Jaffar
authors.forename: Charles M
authors.initials: CM
authors.lastname: Thompson
authors.forename: Kevan
authors.initials: K
authors.lastname: Roberts
authors.forename: Philippe
authors.initials: P
authors.lastname: Diaz
mesh_terms: D000818:Animals; D001402:B-Lymphocytes; D016466:CHO Cells; D006224:Cricetinae; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D005453:Fluorescence; D005456:Fluorescent Dyes / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D006834:Hydrazines / Q000737:chemistry / Q000378:metabolism; D006835:Hydrazones / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D007510:Isatin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D008024:Ligands; D008168:Lung; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D015394:Molecular Structure; D010069:Oxadiazoles / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011714:Pyrans / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists / Q000032:analysis* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: C520846:2-((2,4-dichlorphenyl)amino)-N-((tetrahydro-2H-pyran-4-yl)methyl)-4-(trifluoromethyl)-5-pyrimidinecarboxamide; D005456:Fluorescent Dyes; D006834:Hydrazines; D006835:Hydrazones; D008024:Ligands; C118674:N-(4-nitro-2,1,3-benzoxadiazol-7-yl)-N-methyl-2-aminoacetohydrazide; D010069:Oxadiazoles; D011714:Pyrans; D011743:Pyrimidines; D043885:Receptor, Cannabinoid, CB2; D007510:Isatin