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Today’s drug discovery around G protein-coupled receptors (GPCRs) is quite different from decades ago, when GPCRs weren’t even known to be the target of the newest drugs on the market. Are today’s knowledge-based drug discovery approaches better and faster though? Join your scientific colleagues for this day and a half meeting to debate these questions and more. Learn how the latest functional screening strategies and cutting-edge GPCR crystal structures are/can be applied to drug discovery and development. Also hear case studies around drug candidates developed against specific GPCRs and keep abreast of their progress in the clinic and pharmacological challenges.

WEDNESDAY, NOVEMBER 2

7:00 am Conference Registration and Morning Coffee

Ligand-Biased SIGNALING

8:30 Chairperson’s Opening Remarks

Annette Gilchrist, Ph.D., Assistant Professor, Department of Pharmaceutical Sciences, Midwestern University

8:40 KEYNOTE PRESENTATION:

Harnessing the Functional Selectivity of GPCRs for Drug Discovery

Michel BouvierMichel Bouvier, Ph.D., Professor, Department of Biochemistry, University of Montreal

G protein-coupled receptors can engage multiple signaling cascades that may or may not involve G protein activation. This functional selectivity of GPCRs is controlled by the ligand that binds the receptor. Such ligand-biased signaling can be exploited for the development of new drugs with increased selectivity profiles and less undesirable effects. I present approaches we used involving both BRET-based biosensors and label-free methods that hold promise for large scale drug discovery applications.

9:40 GPCR Biased Ligands: Translating Theory to Improved Therapies

Jonathan Violin, Ph.D., Head of Biology, Trevena

Biased GPCR ligands selectively engage or elude distinct receptor signaling mechanisms, and may provide a strategy for designing safer and more efficacious GPCR-targeted drugs. Two examples illustrate how biased ligands can elicit novel pharmacological profiles: TRV027, a beta-arrestin biased ligand of angiotensin II type 1 receptor, and TRV002, a G protein-biased ligand of the mu opioid receptor. These compounds highlight the concept, mechanism of action, and utility of biased ligands.

10:10 Grand Opening Coffee Break in the Exhibit Hall with Poster Viewing

 

GPCR Screening Challenges

10:40 Talk Title to be Announced

Mark Pausch, Ph.D., Director, in vitro Pharmacology, Merck


11:10 Discovery and Characterization of a Novel Chemical Class of GABA-BR Allosteric Potentiators

Geraldine Parenty, Ph.D., Senior Scientist, in vitro Pharmacology, Addex Pharma

The allosteric modulation of GABA-BRs is offering an attractive and novel approach to identify new drug candidates for the treatment of disorders such as anxiety, depression, schizophrenia, pain or GERD, that are devoid of side effects associated with GABAB receptor agonists (e.g. baclofen), and represent a major advance in the drug discovery process. Addex has recently demonstrated in vivo efficacy of such novel PAMs in pre-clinical models of anxiety, inflammatory pain and osteoarthritis pain models.

11:40 Hit Identification and Hit Assessment for the Orphan G Protein-Coupled Receptor GPR88

Neil Burford, Ph.D., Senior Research Investigator II, Lead Discovery & Profiling, Bristol-Myers Squibb Company

GPR88 is highly expressed in brain regions and is implicated in the modulation of striatal dopamine function. GPR88 knockout mice exhibit a pro-psychotic behavioral phenotype suggesting that GPR88 agonists might be therapeutically beneficial as a treatment for schizophrenia. In this case study, the discovery of surrogate agonists for GPR88 from high throughput screening will be described with emphasis on the challenges associated with screening an orphan GPCR.

12:10 pm Panel Discussion: Which Screening Strategy to Use?

Lisa MinorModerator: Lisa K. Minor, Ph.D., President, In vitro Strategies, LLC

Panelists will present their screening strategy and choice of assays in response to vaious mock drug discovery scenarios presented by the moderator.


Panelists:

Neil Burford, Ph.D., Senior Research Investigator II, Lead Discovery & Profiling, Bristol-Myers Squibb Company

Annette Gilchrist, Ph.D., Assistant Professor, Department of Pharmaceutical Sciences, Midwestern University

Mark Pausch, Ph.D., Director, in vitro Pharmacology, Merck

 

Sponsored by
DiscoverRx
12:40 Luncheon Presentation:

Discovery of Novel, Biased Ligands Using a Suite of PathHunter® and HitHunter® GPCR Screening Platforms

Elizabeth R. Quinn, Ph.D., Senior Product Manager, GPCR Product Portfolio, DiscoveRx Corp.

Although G-protein dependent and independent pathways are often modulated in concert, a number of compounds having differential effects on these pathways have been reported. In order to gain further insight into this, a systematic characterization of GPCR targets and their associated ligands was done using: HitHunter® 2nd messenger signaling, PathHunter® arrestin activation, and PathHunter® receptor internalization. This talk focuses on how functional selectivity may be prevalent across receptor and ligand classes which could lead into discovery of compounds with novel characteristics.

SIGNALING COMPLEXITIES

2:20 Chairperson’s Remarks

Graeme Semple, Ph.D., Vice President, Discovery Chemistry, Arena Pharmaceuticals, Inc.

2:25 7TM Activation Mechanism -- Basis for Structure-based Drug Discovery

Thue Schwartz, Ph.D., Professor, The Novo-Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen

2:55 Regulators of Heterotrimeric G-protein Signaling

David Siderovski, Ph.D., Professor, Director, Chemical Biology, Department of Pharmacology, University of North Carolina at Chapel Hill

I discuss two distinct families of GPCR signaling modulators discovered in my laboratory: the ‘regulators of G-protein signaling’ (RGS) and GoLoco motif protein families. I will survey some of our latest findings on the physiological functions of RGS proteins and examine recent efforts to establish and validate proof-of-principle small molecule modulators of these proteins.

3:25 Networking Refreshment Break in the Exhibit Hall with Poster Viewing

4:05 Small Molecule Modulators of NTSR1 Signalling Exhibit Ligand Bias

Patricia McDonald, Ph.D., Associate Director, Translational Research Institute, Scripps Florida

4:35 Generating Fully Human Antagonistic Antibodies against GPCR Targets

Sergej Kiprijanov, Ph.D., Vice President of Research and Pre-clinical Development, Affitech A/S

Using proprietary CBAS™ technology, Affitech generated a panel of antagonistic antibodies against GPCR targets involved in cancer progression and inflammation. The generated antibodies effectively competed with ligand binding, were able to block ligand-induced signaling and cell migration, and demonstrated high cell killing activity via ADCC. Data showing applicability of the GPCR targeting antibodies for treatment of cancer, inflammatory and autoimmune diseases will be presented.

5:05 Interactive Breakout Discussion Groups

In this interactive session, delegates are invited to choose a breakout topic of interest (listed below) and join the moderated discussion at hand. Participants are encouraged to share examples from their work, vet ideas with peers and be part of a group problem-solving endeavor. We emphasize that this discussion is an informal exchange amongst scientists and is not meant to be, in any way, a corporate or product discussion.

Topic: GPCRs -- Still a Good Target Class?

Moderator: Graeme Semple, Ph.D., Vice President, Discovery Chemistry, Arena Pharmaceuticals, Inc.

• Value of GPCRs compared to other target classes within institutions/companies
• Is the importance of GPCRs in drug development changing?
• Future of this target class

Topic: Membrane Protein Challenges

Moderator: Alexei Yeliseev, Ph.D., Staff Scientist, NIAAA, NIH


• Expression of GPCRs for structural studies
• Stabilization of GPCRs in detergents and lipid bilayers
• Site-specific and stable isotope-labeling

Topic: De-Orphanizing GPCRs

Moderator: Timothy W. Lovenberg, Ph.D., Senior Research Fellow, Johnson & Johnson Pharmaceutical Research and Development, LLC

• Current strategies
• Examples
• Does my ligand bind allosterically?

Sponsored by
CarnaBiosciences
6:15 – 7:15 Welcoming Reception in the Exhibit Hall with Poster Viewing


 

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PREMIER SPONSOR 

Cellecta 

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SPONSORSHIPS & EXHIBITS 

The exhibit hall was sold out in 2013, so please contact us early to reserve your place. To customize your sponsorship or exhibit package for 2014, contact:

Jon Stroup
Business Development Manager
781-972-5483
jstroup@healthtech.com 

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