The objectives of Project I are to create -arrestin-biased dopamine D2R agonist clinical candidates for the treatment of schizophrenia and related disorders, and to create extremely G(1)-biased D2R agonists as chemical probes for elucidating the key signaling pathways essential for antipsychotic efficacy and side-effects. I have the expertise, leadership and motivation necessary to lead this medicinal chemistry project.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19MH082441-08
Application #
8664924
Study Section
Special Emphasis Panel (ZMH1-ERB-C)
Project Start
Project End
Budget Start
2014-05-01
Budget End
2015-04-30
Support Year
8
Fiscal Year
2014
Total Cost
$342,000
Indirect Cost
$117,000
Name
University of North Carolina Chapel Hill
Department
Type
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Rose, Samuel J; Pack, Thomas F; Peterson, Sean M et al. (2017) Engineered D2R Variants Reveal the Balanced and Biased Contributions of G-Protein and ?-Arrestin to Dopamine-Dependent Functions. Neuropsychopharmacology :
Urs, Nikhil M; Peterson, Sean M; Caron, Marc G (2017) New Concepts in Dopamine D2 Receptor Biased Signaling and Implications for Schizophrenia Therapy. Biol Psychiatry 81:78-85
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Wang, Sheng; Wacker, Daniel; Levit, Anat et al. (2017) D4 dopamine receptor high-resolution structures enable the discovery of selective agonists. Science 358:381-386
Arnsten, Amy F T; Girgis, Ragy R; Gray, David L et al. (2017) Novel Dopamine Therapeutics for Cognitive Deficits in Schizophrenia. Biol Psychiatry 81:67-77
Pogorelov, Vladimir M; Rodriguiz, Ramona M; Cheng, Jianjun et al. (2017) 5-HT2C Agonists Modulate Schizophrenia-Like Behaviors in Mice. Neuropsychopharmacology 42:2163-2177
Lansu, Katherine; Karpiak, Joel; Liu, Jing et al. (2017) In silico design of novel probes for the atypical opioid receptor MRGPRX2. Nat Chem Biol 13:529-536
Urs, Nikhil M; Gee, Steven M; Pack, Thomas F et al. (2016) Distinct cortical and striatal actions of a ?-arrestin-biased dopamine D2 receptor ligand reveal unique antipsychotic-like properties. Proc Natl Acad Sci U S A 113:E8178-E8186
Butler, Kyle V; Bohn, Kelsey; Hrycyna, Christine A et al. (2016) Non-Substrate Based, Small Molecule Inhibitors of the Human Isoprenylcysteine Carboxyl Methyltransferase. Medchemcomm 7:1016-1021

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