Proc. Natl. Acad. Sci. USA
Discovery of β-arrestin-biased dopamine D2 ligands for probing signal transduction pathways essential for antipsychotic efficacy.
Allen, J.A., Yost, J.M., Setola, V., Chen, X., Sassano, M.F., Chen, M., Peterson, S., Yadav, P.N., Huang, X.P., Feng, B., Jensen, N.H., Che, X., Bai, X., Frye, S.V., Wetsel, W.C., Caron, M.G., Javitch, J.A., Roth, B.L. and Jin, J.
Notes: This paper explored potential compounds as agonists of dopamine D2 receptor (D2R) with a bias toward β-arrestin signaling. Based on the aripiprazole scaffold, compounds were synthesized and tested in a D2-mediated Gi-coupled isoproterenol-stimulated cAMP production assay using HEK293T cells expressing D2R transfected with pGloSensor™-22F cAMP Plasmid. Assessing β-arrestin recruitment to agonist-stimulated receptors was determined using HTLA cells stably expressing β-arrestin-TEV protease and a tetracycline transactivator-driven luciferase exposed to agonist or D2 test ligand with or without reference agonist. After 18 hours, medium was removed from the cells, 1X Bright-Glo™ Reagent added and luminescence measured. (4518)
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