GPCR-Based Drug Discovery, Part 2 header

About This Conference:

G protein coupled receptors (GPCRs) are attractive targets for pharmacological modulation due to their role in many medically-relevant biological processes. This meeting will present tools and new knowledge that is aiding the discovery of compounds with more precise control of receptor signaling. Case studies of lead compounds progressing (or not) in the drug discovery pipeline will also be included.

Thursday, October 9

11:30 am Registration

1:00 pm Plenary Keynote Program 

Chas BountraChas Bountra, Ph.D., Professor of Translational Medicine & Head, Structural Genomics Consortium, University of Oxford

Martin TolarMartin Tolar, M.D., Ph.D., Founder, President & CEO, Alzheon, Inc.

Andrew L. Hopkins, Andrew L. Hopkins, D.Phil, FRSC, FSB, Chair of Medicinal Informatics and SULSA Research Professor of Translational Biology, Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee

2:45 Refreshment Break in the Exhibit Hall with Poster Viewing

3:45 Chairperson’s Opening Remarks

Jeffrey Brown, Ph.D., Senior Research Investigator II, Department of Experimental Biology and Genomics, Bristol-Myers Squibb

3:55 Discovery of Potent and Selective Inhibitors of CRTH2

Kevin W. Hunt, Ph.D., Associate Director of Drug Discovery, Medicinal Chemistry, Array Biopharma

ARRY-502 is a potent, selective inhibitor of CRTh2, a key GPCR emerging as an effective drug target for allergic asthma. As current asthma therapies do not fully target this pathway, CRTh2 antagonists represent an exciting new approach to enhanced disease control. The preclinical and clinical data to be presented suggest broad applicability of ARRY-502 in the asthma population, as well as in other Th-2 driven diseases.

4:25 Targeting Chemokine Receptors for Inflammation

Dan Dairaghi, Ph.D., Senior Director, Molecular Pharmacology and Biomarkers, ChemoCentyrx

The chemokine system, including chemokines and chemo-attractants, directs inflammatory responses, serving to precisely coordinate immune system cell movement. As drivers of the inflammatory response, chemokines and their receptors present opportunities for the development of new therapies. Each of ChemoCentryx’s novel small molecule drug candidates is designed to target a specific chemokine receptor, thereby blocking the inflammatory response driven by that particular chemokine while leaving

4:55 An Innovative Biochemical Assay Measures Affinities and Rate Constants of CXCR4-Ligand Binding: New Perspectives for GPCRs as Drug Targets 

Manal Chatila, Ph.D., Manager, Strategic Alliance & Business Development, Intana Bioscience

GPCR assay development relies on cellular assays due to solubilization and purification difficulties. Using our fluorescence correlation spectroscopy approach we can bypass these pitfalls and measure Kds and rate constants of GPCR-Ligand interactions and thus allows a comprehensive interaction analysis. Here, we show the establishment of a mix-and-read assay for GFP-labeled CXCR4 as a proof of concept, amenable to extension to other GPCRs.

5:25 Coffee Break in the Foyer

5:40 Oral FSH? Discovery of Oral FSHR (Follicle Stimulating Hormone Receptor) Allosteric Modulators

Henry Yu, Ph.D., Head, Medicinal Chemistry, TocopheRx, Inc.

Follicle-stimulating hormone (FSH), acting on its receptor (FSHR), plays a pivotal role in the stimulation of follicular development and maturation. Multiple injections of FSH are used in clinics for ovulation induction and for in-vitro fertilization. An orally bioavailable FSH mimetics would increase patient convenience and compliance. Our effort leading to orally active positive allosteric modulators (PAM) targeting FSHR will be described. We will present SAR, selectivity, DMPK, and efficacy

6:10 Targeting Melanin Concentrating Hormone Receptors for Obesity: Lessons Learned

Brian J. Murphy, Ph.D., Senior Principal Scientist, Fibrosis Drug Discovery, Bristol-Myers Squibb

This presentation spans SAR optimization to our clinical candidate and proof of principle efforts in humans of MCHR1 antagonists for the treatment of obesity. We found that compounds with slow-off rates/long residence times were required for efficacy. This prompted us to develop a FLIPR-based assay to triage off-rates in a medium throughput mode which greatly facilitated compound selection for more detailed kinetic work and in vivo testing.

6:40 Close of Day

7:00 Dinner Short Course: Introduction to Allosteric Modulators and Biased Ligands of GPCRs (SC12)*

Michel Bouvier, Ph.D., Professeur, Department of Biochemistry, University of Montréal
Stephan Schann, Ph.D., Head, Research, Domain Therapeutics SA

*Separate registration is required

Friday, October 10

7:30 am Registration

8:00 Interactive Breakfast Breakout Discussion Groups

This interactive session provides conference delegates and speakers an opportunity to choose a specific roundtable discussion group to join. Each group has a moderator to ensure focused discussions around key issues within the topic. This format allows participants to meet potential collaborators, share examples from their work, vet ideas with peers, and be part of a group problem-solving endeavor. The discussions provide an informal exchange of ideas and are not meant to be a corporate or specific product discussion.

GPCR Ligands: Implications and Methods for Optimizing Receptor Residence Times

Brian J. Murphy, Ph.D., Senior Principal Scientist, Fibrosis Drug Discovery, Disease Sciences and Biologics R&D, Bristol-Myers Squibb

  • When is a long receptor residence time an optimal property for GPCR ligands?
  • Can one monitor off-rates during a GPCR SAR campaign to drive SAR in real time?
  • Is there predicable SAR for off-rate optimization for GPCR ligands?
  • Is monitoring off-rates in real time worth the effort ?

Challenges for CNS-Targeted GPCR-acting Compounds

Walter Kostich, Ph.D., Formerly Senior Research Investigator, Exploratory Biology and Genomics, Bristol-Myers Squibb Company

  • Promise and challenges of allosteric modulators
  • Blood brain barrier issues
  • Translating preclinical tools to clinical efficacy

Recombinant vs Native Screening Approaches for GPCRs

Andrew Alt, Ph.D., Senior Research Investigator, Lead Discovery, Bristol-Myers Squibb

  • Should GPCR screening be carried out using primary cells/tissues?
  • Do assays utilizing natively expressed receptor systems have sufficient sensitivity for hit identification (specifically for allosteric modulators)?
  • Can ligand-biased signaling be effectively studied using recombinant systems?
  • Can screening using native cells lines improve translatability and get us to in vivo efficacy faster?


9:00 Chairperson’s Remarks

Dario Doller, Ph.D., Director, Discovery Chemistry & DMPK, Lundbeck Research USA

9:10 Complexities in Allosteric Modulation of the mu-Opioid Receptor

John Traynor, Ph.D., Professor of Pharmacology, University of Michigan Medical School

The orthosteric binding site of the opioid mu-receptor (MOPr) is the major target for all clinically used opioid analgesics. We have recently discovered the first positive allosteric modulator (PAM) of MOPr. Identification of MOPr-PAMs provides a new approach to the development of novel analgesic agents. I will discuss the complex probe-dependent nature of the MOPr-PAM activity and the potential mechanism of allosteric modulation.

9:40 Identification of a Novel D1 Dopamine Receptor PAM Binding Site

Jeffrey Brown, Ph.D., Senior Research Investigator II, Department of Experimental Biology and Genomics, Bristol-Myers Squibb

D1 positive allosteric modulators (PAMS) have therapeutic potential for the treatment of cognitive disorders. The current studies describe the identification of potent selective D1 PAMS. Interestingly, these D1 PAMS showed selectivity for the human vs. rodent D1 receptors. We employed D1 human/rodent chimeras as well as high-throughput mutagenesis to map the potential amino acids involved in the activity and species selectivity of these D1 PAMS.

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


10:55 Structural Basis for Allosteric Modulation of GPCRs

Ron DrorRon Dror, Ph.D., Associate Professor, Computer Science, Stanford University

Using atomic-level simulations, we determined the binding sites and binding modes of multiple allosteric modulators of a muscarinic GPCR. Simulations also revealed mechanisms that contribute to positive and negative allosteric modulation of classical ligand binding. These findings, which we validated experimentally, provide an initial structural basis for the rational design of allosteric GPCR modulators.

11:25 Impact of Diverse Modes of Efficacy on in vivo Actions of Allosteric Modulators of GPCRs

P. Jeffrey ConnP. Jeffrey Conn, Ph.D., Professor of Pharmacology, Director, Vanderbilt Center for Neuroscience Drug Discovery

Allosteric modulators of the metabotropic glutamate (mGlu) receptors provide excellent examples of the multiple modes of efficacy that can be achieved with allosteric modulators of GPCRs. The diversity of mGlu allosteric modulators now available are providing fundamental new insights into the impact of stimulus bias, actions on homodimer versus heterodimer forms of the receptors, and unique modes of efficacy of structurally related allosteric modulators.

11:55 Unbiased Approaches to Study Ligand-Biased Signaling and GPCR Functional Selectivity

Michel BouvierMichel Bouvier, Ph.D., Professeur, Department of Biochemistry, University of Montréal

It is now well established that a given GPCR can engage multiple G protein-dependent and independent signaling pathways. This pluri-dimensionality of efficacy gave rise to the concepts of functional selectivity and ligand-biased signaling that open great opportunities for drug discovery but also present important technical challenges. We will discuss the development of BRET-based biosensors as well as label-free approaches that can be used as unbiased means to map the signaling repertoire of G

12:25 pm Novel Melanin-Concentrating Hormone Receptor-1 (MCH1) Antagonists: From Concept to Clinic 

Pete Guzzo, Ph.D., Director, Drug Discovery, AMRI

Clinical development of drugs for CNS disorders can be a challenging and risky endeavor. In this presentation we look at the steps required to move a preclinical candidate compound into clinical development. We use the case study of ALB-127158(a), an MCH1 receptor antagonist for the treatment of obesity via a central mechanism.

12:40 GPCR Allosteric Compound Selectivity through Large Scale Profiling
Kimberly Italiano, Scientist, Cell-Based Assay Team Lead, Eurofins Discovery Services
One expected advantage of allosteric compounds is a higher degree of selectivity relative to orthosteric compounds. To empirically explore this hypothesis, we profiled twenty-seven different compounds reported to be GPCR allosteric modulators against a panel of over 156 GPCRs using cell based assays to detect agonist, positive allosteric modulation and inhibitory activities. 

12:55 Session Break

1:05 Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own

1:45 Session Break


1:55 Chairperson’s Remarks

John Traynor, Ph.D., Professor of Pharmacology, University of Michigan Medical School

2:00 Structures of the Nociceptin/Orphanin FQ Receptor (NOP/ORL1): Black Sheep of the Opioid Receptor Family

Aaron Thompson, Ph.D., Staff Scientist, Molecular and Cell Biology Department, Scripps Research Institute

Despite high sequence similarity with classical opioid G protein-coupled receptor subtypes, the nociceptin/orphanin FQ (N/OFQ) peptide receptor (NOP/ORL1) displays markedly distinct pharmacology.  Crystal structures reveal substantial conformational differences in the orthosteric pocket regions between NOP and the “classical” opioid receptors resulting in the distinct ligand preference. NOP’s emerging pharmacore provides a new structural template for the design of novel, selective ligands.

2:30 Targeting a Family B GPCR: CGRP Receptor Antagonists for Migraine

Ian Bell, Ph.D., Principal Scientist, Discovery Chemistry, Merck Research Laboratories

Calcitonin gene-related peptide receptor antagonists (CGRP-RAs) have demonstrated clinical efficacy for acute treatment of migraine. In general, these agents have shown similar clinical responses to triptans with a reduced incidence of adverse events. Interestingly, the precise mechanism of action of CGRP-RAs, in particular whether they act centrally or peripherally, continues to be a matter of debate. Our program to develop novel, orally bioavailable CGRP-RAs and our efforts to elucidate their

3:00 Refreshment Break in the Exhibit Hall with Poster Viewing

3:30 Targeting mGluR4 for Parkinson’s Disease

Francois Conquet, Ph.D., CEO, Prexton Therapeutics

One of the major objectives of research into new treatments for Parkinson’s disease (PD) is to find alternatives to the stimulation of the dopaminergic system through L-DOPA and dopamine agonists, as long-term use of these established treatments are responsible for severe side effects. Prexton is developing positive allosteric modulators of the metabotropic glutamate receptor mGluR4 for the treatment of motor symptoms of PD.

4:00 Chemical Biology of mGlu4 Receptor Activation: Dogmas, Challenges, Strategies and Opportunities

Dario Doller, Ph.D., Director, Discovery Chemistry & DMPK, Lundbeck Research USA

L-glutamate exerts its physiological functions acting through transmembrane ion channels and G protein-coupled receptors (GPCRs). Progress using allosteric modulators to evaluate the therapeutic potential of mGlu4 receptor activation continues. Our aim is to present a number of reflections on recent developments and unique challenges that point out the singularities in the Chemical Biology of mGlu4 positive allosteric modulators.

4:30 The Signaling of Adhesion GPCR GPR56 in Neural Development and Diseases

Xianhua Piao, M.D., Ph.D., Assistant Professor of Pediatrics, Children's Hospital Boston, Harvard Medical School

Being a family of noncanonical seven transmembrane spanning (7TM) receptors, adhesion GPCRs have an exceptionally long extracellular N-terminal region and juxtamembrane GPCR autoproteolysis-inducing (GAIN) domain. Most adhesion GPCRs undergo GAIN domain-mediated autoproteolytic process at the GPCR proteolysis site (GPS) to generate an N- and a C-terminal fragment. GPR56, a member of adhesion GPCRs family, plays an important role in neural development and diseases. Identification and Characterization of GPR56 endogenous ligand(s) pave the way for future drug discovery.  

5:00 Close of Conference


Suggested Event Package:

October 7

*Short Course: GPCR Structure-Based Drug Discovery 

*Short Course: Targeting of GPCRs with Monoclonal Antibodies 

October 8-9: GPCR-Based Drug Discovery Conference 

October 9:

*Short Course: Introduction to Allosteric Modulators and Biased Ligands of GPCRs 

October 9-10: GPCR-Targeted Therapeutics Conference 

*Separate registration is required

DOT Hub Icon 

Japan-Flag Korea-Flag China-Simplified-Flag China-Traditional-Flag 


2014 Discovery on Target Brochure  







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

2014 Discovery On Target CAG