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Center for Drug Discovery conducts multidisciplinary research aimed at the discovery of new therapeutic medications

About Center for Drug Discovery

The CDD was founded in 2003 by and is directed by Alexandar Makriyannis, the Behrakis Chair in Pharmaceutical Biotechnology. The CDD is directed to:

  • Develop novel methodologies to improve drug discovery
  • Discover new medications to satisfy important medical needs
  • Train students and post-doctoral fellows in the art and science of drug discovery
  • Collaborate intensively with the biotechnology and pharmaceutical industries as well as leading clinical centers

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Cell - Volume 167, Issue 3, p750–762.e14, 20 October 2016
Crystal Structure of the Human Cannabinoid Receptor CB1

Cannabinoid receptor 1 (CB1) is the principal target of Δ9-tetrahydrocannabinol (THC), a psychoactive chemical from Cannabis sativa with a wide range of therapeutic applications and a long history of recreational use. CB1 is activated by endocannabinoids and is a promising therapeutic target for pain management, inflammation, obesity, and substance abuse disorders. Here, we present the 2.8 Å crystal structure of human CB1 in complex with AM6538, a stabilizing antagonist, synthesized and characterized for this structural study. The structure of the CB1-AM6538 complex reveals key features of the receptor and critical interactions for antagonist binding.

Nature 547, 468–471 (27 July 2017)
Crystal structures of agonist-bound human cannabinoid receptor CB1

The cannabinoid receptor 1 (CB1) is the principal target of the psychoactive constituent of marijuana, the partial agonist Δ9-tetrahydrocannabinol (Δ9-THC)1. Here we report two agonist-bound crystal structures of human CB1 in complex with a tetrahydrocannabinol (AM11542) and a hexahydrocannabinol (AM841) at 2.80 Å and 2.95 Å resolution, respectively. The two CB1–agonist complexes reveal important conformational changes in the overall structure, relative to the antagonist-bound state2, including a 53% reduction in the volume of the ligand-binding pocket and an increase in the surface area of the G-protein-binding region. In addition, a ‘twin toggle switch’ of Phe2003.36 and Trp3566.48 (superscripts denote Ballesteros–Weinstein numbering3) is experimentally observed and appears to be essential for receptor activation.

Dr. Alexandros Makriyannis

Director


Dr. David Janero

Deputy Director


Shawntelle Dillon

Assistant Director


Dr. Raymond Booth

Associate Director


Brett Greene

Research Administrator