Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Program--Cooperative Agreements (U19)
Project #
4U19MH082441-10
Application #
9069981
Study Section
Special Emphasis Panel (ZMH1)
Project Start
Project End
Budget Start
2016-05-01
Budget End
2017-04-30
Support Year
10
Fiscal Year
2016
Total Cost
Indirect Cost

  Institution

Name
University of North Carolina Chapel Hill
Department
Type
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599

  Publications

Che, Tao; Majumdar, Susruta; Zaidi, Saheem A et al. (2018) Structure of the Nanobody-Stabilized Active State of the Kappa Opioid Receptor. Cell 172:55-67.e15
Wang, Sheng; Che, Tao; Levit, Anat et al. (2018) Structure of the D2 dopamine receptor bound to the atypical antipsychotic drug risperidone. Nature 555:269-273
Rose, Samuel J; Pack, Thomas F; Peterson, Sean M et al. (2018) Engineered D2R Variants Reveal the Balanced and Biased Contributions of G-Protein and ?-Arrestin to Dopamine-Dependent Functions. Neuropsychopharmacology 43:1164-1173
McCorvy, John D; Butler, Kyle V; Kelly, Brendan et al. (2018) Structure-inspired design of ?-arrestin-biased ligands for aminergic GPCRs. Nat Chem Biol 14:126-134
McCorvy, John D; Wacker, Daniel; Wang, Sheng et al. (2018) Structural determinants of 5-HT2B receptor activation and biased agonism. Nat Struct Mol Biol 25:787-796
Peng, Yao; McCorvy, John D; Harpsøe, Kasper et al. (2018) 5-HT2C Receptor Structures Reveal the Structural Basis of GPCR Polypharmacology. Cell 172:719-730.e14
Wacker, Daniel; Wang, Sheng; McCorvy, John D et al. (2017) Crystal Structure of an LSD-Bound Human Serotonin Receptor. Cell 168:377-389.e12
Wacker, Daniel; Stevens, Raymond C; Roth, Bryan L (2017) How Ligands Illuminate GPCR Molecular Pharmacology. Cell 170:414-427
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
Pappas, Andrea L; Bey, Alexandra L; Wang, Xiaoming et al. (2017) Deficiency of Shank2 causes mania-like behavior that responds to mood stabilizers. JCI Insight 2:

Showing the most recent 10 out of 136 publications