Discovery on Target
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GPCR-Based Drug Discovery - Part 2 Header

G protein-coupled receptors (GPCRs) have steadily remained an important target class for drug discovery because of the myriad of biological processes they initiate as transducers of extracellular signals to inside the cell. However, they have always been and still remain a complex target class. Their multi-membrane spanning structure makes them difficult to isolate. Their ability to couple to various intracellular messengers (G proteins and other proteins) complicates interpretation and measurement of downstream signaling.

This two-part meeting enables discovery biologists and chemists to share progress, advances and new strategies in discovering, designing and optimizing GPCR-targeted compounds as well as hear about new work from academia that sheds light on the pharmacological complexities of this receptor class. Updates and challenges of GPCR-targeted compounds advancing in the drug development pipeline will also be a part of the agenda. 

Part Two: 

The second meeting in the set, Part 2: Signaling and Pharmacological Complexities, explores the unique aspects of GPCR signaling which makes the receptors such challenging yet fruitful targets. With the difficulties of targeting GPCRs also come multiple avenues for their pharmacological modulation. Insights on receptor trafficking, modifications, desensitization and selective/biased coupling and how that impacts design of GPCR-targeted compounds will be discussed. Case studies of GPCR-targeted compounds advancing in preclinical or clinical development, including biased ligands and allosteric modulators, will also be featured. 

Final Agenda


• September 19 Short Course: GPCR Structure-Based Drug Discovery

• September 20-21 Conference: GPCR-Based Drug Discovery - Part 1

• September 21-22 Conference: GPCR-Based Drug Discovery - Part 2

• September 21 Short Course: Introduction to Allosteric Modulators

Day 1 | Day 2 | Download Brochure

Wednesday, September 21

11:20 am Conference Registration Open

11:25 Enjoy Lunch on Your Own

2:40 Refreshment Break in the Exhibit Hall with Poster Viewing

GPCR Complexities: Allosterism, Biased Signaling and More

3:20 Chairperson’s Opening Remarks

Annette Gilchrist, Ph.D., Professor, Pharmacology, Midwestern University

3:35 Directing Opioid Receptor Signaling to Improve Analgesic Therapies

Laura M. Bohn, Ph.D., Professor, Departments of Molecular Therapeutics & Neuroscience, The Scripps Research Institute

GPCRs propagate signals via interactions with multiple effectors, including G proteins and {beta}arrestins. GPCRs in different contexts, such as different neuronal populations or different cellular compartments, can couple to different effectors. We are finding that opioid receptor ligands that promote signaling towards G protein signaling over {beta}arrestin recruitment in vitro can be used to dissociate from analgesic responses and certain side effects in vivo.

4:05 Discovery of Non-Desensitizing, Selective CB2 Agonists

David J. Unett, Ph.D., Vice President, Receptor Pharmacology, Arena Pharmaceuticals

Despite years of intense research, clinical development of cannabinoid CB2 receptor agonists has met with little success. Many widely employed tool compounds exhibit modest selectivity and efficacy, perhaps providing misleading results in preclinical models. Additionally, our data suggest that agonists lacking robust CB2 receptor efficacy may rapidly lose efficacy in vivo. A characterization of potent, highly selective and efficacious CB2 agonists will be presented.

PerkinElmer NEW 20094:35 360 Degree Characterization of GPCR Function through Ligand Binding, Functional and Phenotypic Analyses

Roger Bosse, Ph.D., Senior Market Segment Leader, PerkinElmer

We will present several examples showing how combining ligand binding, functional and phenotypic analyses, leads to the discovery and development of an entirely new generation of GPCR drugs including allosteric regulators, inverse agonists and drugs targeting hetero-oligomeric complexes.

5:05 Refreshment Break in the Exhibit Hall with Poster Viewing

5:40 Positive Allosteric Modulators of mGlu4 for the Treatment of Parkinson’s Disease: From HTS to Pre-Clinical Leads

Corey R. Hopkins, Ph.D., Associate Professor, Department of Pharmaceutical Sciences, University of Nebraska Medical Center 

Disorders of the CNS remain some of the most elusive targets for the pharmaceutical industry and academic researchers to tackle. Although Parkinson’s disease (PD) is the second most common neurodegenerative disease, no effective long term treatment or cure has been developed. Utilizing a functional HTS and medicinal chemistry approach, we have discovered a novel series of PAMs of the metabotropic glutamate receptor 4 (mGlu4).

6:10 Deciphering the Molecular Dynamics and Conformation of GPR40 Agonists

Gayathri Swaminath, Ph.D., Principal Scientist, Metabolic Disorders, Amgen

GPR40 is a G protein–coupled receptor highly expressed in ß-cells and activated by long-chain fatty acids. We have previously shown that GRP40 agonists act as allosteric agonists to the endogenous ligand and identified multiple binding sites. Recently, we used the crystal structure to predict the binding sites along with the mutagenesis data. Furthermore the computational modelling studies indicate that the allosteric agonists sample different conformations of the receptor.

6:40 End of Day

Day 1 | Day 2 | Download Brochure

Thursday, September 22

7:30 am Registration Open and Morning Coffee


8:30 Chairperson’s Remarks

Heidi Hamm, Ph.D., Professor, Department of Pharmacology, Vanderbilt University Medical Center

8:45 FEATURED PRESENTATION: GPCRs in Cancer: An Untapped Opportunity

Paul Insel, M.D., Distinguished Professor, Pharmacology and Medicine, University of California San Diego

GPCRs are the most common drug targets but have largely been ignored as therapeutic targets in cancer, other than endocrine-driven tumors, even though GPCRs can regulate many features of the malignant phenotype. Thus, GPCRs

may be useful targets directed at cancer cells themselves but in addition, in cells of the tumor microenvironment—including in pancreatic cancer, a tumor in desperate need of new therapies.

9:15 Desensitization of Cardiac Adrenergic Receptor Signaling through Receptor Cross-Talk

Kevin Xiang, Ph.D., Professor, Pharmacology, University of California Davis

A growing list of cell receptors, including GPCRs, RTKs, and cytokine receptors, impair cardiac adrenergic receptor via both GRKs and second messenger-dependent kinases. Here, I will focus on the impacts of hyperinsulinemia on development of cardiac dysfunction associated with Type-2 diabetes and obesity, and discuss the phosphodiesterase 4D in the cross talk between insulin receptor and adrenergic receptor in heart.

9:45 Drug Discovery with an Orphan GPCR

Alexander Gragerov, Ph.D., Senior Director of Research, Discovery, Omeros Corp.

We previously identified small molecules interacting with 54 class A orphan GPCRs. We now show that these compounds functionally affect receptors and could be used to initiate drug discovery. A case of an orphan GPCR linked to autoimmune disorders will be presented. It will involve effects of receptor-specific compounds on signaling, cell activity, and animal models.

10:15 Coffee Break in the Exhibit Hall with Poster Viewing and Poster Competition Winner Announced

11:10 Discovery of the First Orally Bioavailable GPR39 Agonists

Vidya Kunjathoor, Ph.D., Scientist, Cardiovascular & Metabolic Disease Area, Novartis Institutes for BioMedical Research, Inc.

We report on the identification of highly potent and orally bioavailable GPR39 agonists in mice. The compound was found in a phenotypic screening campaign and was transformed into compound 2 with good activity on both the rat and human GPR39 receptor. This compound was further optimized to improve ligand efficiency and pharmacokinetic properties to yield GPR39 agonists for the potential oral treatment of type 2 diabetes.

11:40 CXCR4 Cyclic Peptide Antagonists for Cancer

Sheng Bin Peng, Ph.D., Group Leader and Senior Research Advisor, Eli Lilly & Co.

We present on our anti-CXCR4 cyclic peptide inhibitor that is now in Phase 2 clinical studies for human hematological malignancies.

12:10 pm Sponsored Presentation (Opportunity Available)

12:40 Session Break

12:50 Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own

1:30 Refreshment Break in the Exhibit Hall with Poster Viewing


2:15 Chairperson’s Remarks

Irina Kufareva, Ph.D., Project Scientist, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego

2:20 FEATURED PRESENTATION: Arrestin/Rhodopsin Crystal Structure and Implications for Drug Design

H. Eric Xu, Ph.D.,Professor, Cancer Research, Van Andel Institute (VAI)

I present the work of our team on using SLAC’s Linac Coherent Light Source (LCLS), the world’s first hard X-ray free electron laser, to generate the first three-dimensional map of arrestin while it was linked with a GPCR. This capability allowed us to create a three-dimensional image of the arrestin-rhodopsin complex at an atomic level—a much higher resolution than is possible with conventional X-ray technology.

2:50 Biasing Beta2-Adrenergic Receptor Signaling

Jeffrey L. Benovic, Ph.D., Professor and Chair, Department of Biochemistry & Molecular Biology, Thomas Jefferson University

GPCRs interact with three families of proteins in a ligand-dependent manner: G proteins, GRKs and arrestins. These interactions play an essential role in regulating GPCR signaling, trafficking and degradation. I will discuss recent strategies that we have used to bias b2-adrenergic receptor signaling to promote Gs bias to regulate airway function and arrestin bias to regulate cardiovascular function.

3:20 Session Break

3:30 GPCR-Mediated G Protein Activation

Heidi Hamm, Ph.D., Professor, Department of Pharmacology, Vanderbilt University Medical Center

GPCR mediated heterotrimeric G protein activation is an obligate step in signal transduction. Our laboratory has used biophysical approaches to show that GPCRs open up a binding site during activation that interacts with Gα’s alpha 5 (α5) helix leading to a rigid body rotation and translation of this helix. The repositioned α5 helix changes its hydrophobic interactions with the core of the protein, leading to allosteric changes, nucleotide release and G protein activation.

4:00 Small Molecule Targeting of G Protein β/γ Subunit Signaling

Alan V. Smrcka, Ph.D., Professor, Pharmacology and Physiology, University of Rochester School of Medicine

Our laboratory has identified a number of small molecules that inhibit various aspects of G β/γ subunit function. This presentation will discuss the biochemical basis for the mechanism of action of these compounds, their pharmacological efficacy in various preclinical models of disease, and their utility in the dissection of GPCR signaling pathways.

4:30 Extended cAMP GPCR-Generated Signaling

Thomas J. Gardella, Ph.D., Associate Professor, Medicine, Massachusetts General Hospital, Harvard

5:00 Close of Conference

Day 1 | Day 2 | Download Brochure

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Final Agenda Now Available









The exhibit hall was sold out in 2015, so please contact us early to reserve your place. To customize your sponsorship or exhibit package for 2016, contact:

Jon Stroup
Sr. Business Development Manager






Next-Generation Histone Deacetylase Inhibitors

Strategies for Tackling Rare Genetic Diseases

Understanding CRISPR: Mechanisms and Applications

Autoimmunity – Small Molecule Approaches

NK Cell-Based Cancer Immunotherapy

Medical Dermatology Therapeutic R&D and Technical Innovation



Targeting Histone Methyltransferases and Demethylases

Targeting the Ubiquitin Proteasome System

Targeting the Microbiome
– Part 1

GPCR-Based Drug Discovery - Part 1

Advances in Gene Editing and Gene Silencing – Part 1

Gene Therapy Breakthroughs

Antibodies Against Membrane Protein Targets – Part 1

Targeting Cardio-Metabolic Diseases

Targeting Ocular Disorders


Targeting Epigenetic Readers and Chromatin Remodelers

Kinase Inhibitor Discovery

Targeting the Microbiome
– Part 2

GPCR-Based Drug Discovery - Part 2

Advances in Gene Editing and Gene Silencing – Part 2

Translating Cancer Genomics

Antibodies Against Membrane Protein Targets – Part 2

Metabolomics in Drug Discovery

TRAINING SEMINAR: Data Visualization


Monday, September 19
8:00 - 11:00 am

(SC1) Immunology Basics for Chemists

(SC2) Designing Peptide Therapeutics for Specific PPIs

(SC3) Phenotypic Screening and Chemical Probe Development

(SC4) Medical Dermatology Therapeutic R&D and Technical Innovation - Part 1

Monday, September 19
2:00 - 3:00 pm

(SC5) GPCR Structure-Based Drug Discovery

(SC6) RNA as a Small Molecule Drug Target

(SC7) Using IP Landscape Studies to Improve Your Confidence

(SC8) Medical Dermatology Therapeutic R&D and Technical Innovation - Part 2

Monday, September 19
3:30 - 6:30 pm

(SC9) Targeting of GPCRs with Monoclonal Antibodies

(SC10) Introduction to Targeted Covalent Inhibitors

(SC11) Contact Lens Drug Delivery Systems

(SC12) Introduction to Gene Editing

Monday, September 19
7:00 - 9:30 pm

(SC13) Convergence of Immunotherapy and Epigenetics for Cancer Treatment

Wednesday, September 21
7:00 - 9:30 pm

(SC14) Cancer Metabolism: Pathways, Targets and Clinical Updates

(SC15) Introduction to Allosteric Modulators and Biased Ligands of GPCRs

(SC16) Functional Screening Strategies Using CRISPR and RNAi

(SC17) Challenges and Opportunities in DNA Methyl Transferase (DNMT) Inhibitors as Therapeutics