Biased ligands in Drug Discovery – the case of TRV027

Supported by:

30 June 2015

About this webinar

Ligand bias is a well-established concept in the GPCR research field that is beginning to emerge as a means to optimise GPCR targeted drug design. Most approved medications that target GPCRs act as either agonists or antagonists of heterotrimeric G protein and β-arrestin pathways. In many cases, this classical signalling paradigm leads to both efficacy and on-target adverse events. Biased GPCR ligands have the ability to activate or inhibit with greater selectivity one of the two downstream effector proteins and its subsequent signalling cascades. The goal of this webinar is to illustrate in vitro characterisation of GPCR ligand bias and its translation to in vivo proof-of concept using TRV027, an AT1R modulator, as an exemplar biased ligand.

Learning outcomes

• Review of GPCR signalling
• Introduction to concept of ligand bias and quantification thereof
• Utility of 2nd messenger assays in GPCR drug discovery
• Pre-clinical biased ligand proof-of-concept

Guest Speakers

William Gowen-MacDonald

Scientist, Trevena, Inc.

Graduated from University of Colorado in 2008 with a bachelor’s degree in molecular, cellular and developmental biology. Joined Trevena’s research team in 2009 as an in vitro biologist focused on biased ligand discovery through both the deployment and expansion of Trevena’s Advanced Biased Ligand Explorer (ABLE™) platform.

Nicolas Pierre

Global Brand Manager, Cisbio Bioassays

Co-Graduated from University Polytech Engineering school in 2007 and University of Oklahoma with a master in Engineering. Joined Cisbio US, Boston area, first as an assay Development Scientist, spent a year as a field Application specialist, before becoming Custom Project Manager for 3 years. Now, Global Brand Manager, responsible for key products lines: GPCR and Biomarkers.

Special Guest: Terry Kenakin Ph.D.

Professor, Department of Pharmacology, University of North Carolina School of Medicine

Dr. Kenakin has been involved in drug discovery for over 30 years. Prior to joining the UNC Department of Pharmacology,  Terry Kenakin received a Ph.D. in Pharmacology at the University of Alberta, Edmonton Canada, then completed a post-doctoral Fellowship at University College London, U.K.  He then joined Burroughs-Wellcome as an associate Scientist. From there he continued working in drug discovery at Glaxo Inc., GlaxoWellcome and GlaxoSmithKline.