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Illuminating The Druggable GPCR-OME


Bryan Roth, M.D., Ph.D.
Michael Hooker Distinguished Professor of Protein Therapeutics and Translational Proteomics
Department of Pharmacology
School of Medicine
University of North Carolina, Chapel Hill

Brian Shoichet, Ph.D.
Professor
Department of Pharmaceutical Chemistry
University of California
San Francisco


Contacts

Bryan Roth: @zenbrainestM
Roth Lab: @RothlabUNC

Overview

Collaborative work by Dr. Bryan Roth and Dr. Brian Shoichet focuses on illuminating the druggable GPCR-ome by two-pronged approach of empirical screening of drugs followed by computational screening against modeled structures of the GPCR to produced optimized lead compounds. Their work has led to discovery of molecule “ogerin” binding previously orphaned, GPR68.
Additional collaborators include:
Jian Jin, Ph.D. lab (MSSM) - http://labs.icahn.mssm.edu/jinlab/
Pablo Ariel, PhD from UNC Light Sheet Core - https://www.med.unc.edu/microscopy
Dale Cowley, PhD from UNC Mouse Genetics Core - https://www.med.unc.edu/amc/services/å

NIH grant number: 1U24 DK116195-01




DRGC-GPCR publications:

1. Discovery of new GPCR ligands to illuminate new biology.
Roth BL, Irwin JJ, Shoichet BK.
Nat Chem Biol. 2017 Nov;13(11):1143-1151. doi: 10.1038/nchembio.2490. Epub 2017 Oct 18.

2. In silico design of novel probes for the atypical opioid receptor MRGPRX2.
Lansu K, Karpiak J, Liu J, Huang XP, McCorvy JD, Kroeze WK, Che T, Nagase H, Carroll FI, Jin J, Shoichet BK, Roth BL.
Nat Chem Biol. 2017 May;13(5):529-536. doi: 10.1038/nchembio.2334. Epub 2017 Mar 13.
 
3. Allosteric ligands for the pharmacologically dark receptors GPR68 and GPR65.
Huang XP, Karpiak J, Kroeze WK, Zhu H, Chen X, Moy SS, Saddoris KA, Nikolova VD, Farrell MS, Wang S, Mangano TJ, Deshpande DA, Jiang A, Penn RB, Jin J, Koller BH, Kenakin T, Shoichet BK, Roth BL.
Nature. 2015 Nov 26;527(7579):477-83. doi: 10.1038/nature15699. Epub 2015 Nov 9
 
4. How Ligands Illuminate GPCR Molecular Pharmacology.
Wacker D, Stevens RC, Roth BL.
Cell. 2017 Jul 27;170(3):414-427. doi: 10.1016/j.cell.2017.07.009.