1日目 | 2日目 |

現在のGタンパク質共役受容体（GPCR）に関する創薬は数十年前とはかなり異なっています。当時は、GPCRが市場において最新の薬剤の標的であることがまだ知られていませんでした。今日の知識に基づく創薬方法は改善され、迅速なものになっているのでしょうか。この半日のイベントに参加し、これらの疑問などについて話し合ってください。最新の機能的スクリーニング戦略や最新のGPCR結晶構造をどのように、創薬や薬剤開発に応用される／できるのかを学んでください。また、特定のGPCRに対して開発された薬剤候補に関するケーススタディを聴き、臨床上および薬理学的課題についてその最新動向を探ってください。

2011年11月2日（水）

7:00 am Conference Registration and Morning Coffee

リガンドバイアス信号伝達

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 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スクリーニングにおける課題

10:40 Talk Title to be Announced

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

11:10 Sponsored Presentations (Opportunities Available)

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?

Moderator: 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.

Sponsored by
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.

信号伝達複合体

2:20 Chairperson’s Remarks

2:25 Talk Title to be Announced

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 Antiparkinsonian and Anxiolytic Effects of a Novel Chemical Class of Positive Allosteric Modulators of Metabotropic Glutamate Receptor 4

Brice Campo, Ph.D., Group Leader, In vitro Pharma, Addex

Addex will disclose a novel chemical scaffold with a pharmacophore and structure activity relationship that is completely different from what it’s known in the field. We also describe a proof-of-concept compound demonstrating efficacy in pre-clinical models of PD and anxiety disorders without any side effects(dyskenisias)associated with the existing frontline therapy l-DOPA. This work has been done in collaboration with Merck.

4:35 Generating Fully Human Antagonistic Antibodies against GPCR Targets

Sergej Kiprijanov, Ph.D., Vice President of Research and Preclinical 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

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

1日目 | 2日目 |

Suggested Event Package Nov. 1 Short Courses (SC2) Biomarkers Ion Channel Assays for Safety Screening - View Agenda Overview of current and emerging assays and methodologies Use of automation and high-throughput techniques Comparison of platforms and applications Factors affecting sensitivity and specificity AND (SC6) Label Free Assays for GPCRs and Safety and Metabolic Profiling - View Agenda Types of label-free platforms and their pros and cons Label-free, cell based assays for GPCRs Tyrosine kinase-based label free assays for selectivity considerations Metabolic profiling applications (measuring pH and oxygen consumption changes) Nov. 2-3 Conferences GPCR-Based Drug Discovery Nov. 3-4 Conferences Targeting the PI3K Pathway - View agenda OR Allosteric Modulators - View agenda