Protein-Protein Interactions as Drug Targets

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12:30 pm Registration

1:30 Chairperson’s Opening Remarks

1:40 Identifying Extracellular Protein Interactions Using a Secreted Protein Microarray Platform

Lino Gonzalez, Ph.D., Scientist, Protein Chemistry, Genentech, Inc.

Technologies for identifying protein-protein interactions are largely biased towards intracellular binding partners. To address extracellular protein interactions, we have developed a secreted-protein microarray and validated its use as a fast and robust method for identifying receptor-ligand interactions. A set of eighty-nine immunoglobulin-domain receptors was screened and used to establish a scoring and specificity algorithm that revealed top hits as known binding partners and several new interactions for functional validation.

2:10 Assessing Druggability of Protein Interactions using Pocket Optimization

John Karanicolas, Ph.D., Assistant Professor, Center for Bioinformatics and Department of Molecular Biosciences, The University of Kansas

2:40 An Allosteric Model to Describe the Interactions between RBP4, TTR and RBP4-Binding Ligands

Peter Coward, Ph.D., Principal Scientist, Amgen, Inc.

Sponsored by
Asinex logo
3:10 Innovative Approaches to Library Design that Meet the Challenge of PPI Drug Discovery

Dmitry Genis, Ph.D., CEO, Asinex Ltd, Russia

Although there has been moderate success in screening compounds against well-established drugable targets, for PPIs (along with other newly emerging screening targets), the identification of highly active compounds is proving to be elusive. In this talk, the library design factors that have contributed to the lack of suitable compounds will be analyzed and a rational approach to the design of drug-like modulators of PPI will be described. Particular attention will be paid to an important aspect of ASINEX’s design process which involves the emphasis on important drug-like trends found both in natural products and known PPI ligands. 

3:40 Networking Refreshment Break in the Exhibit Hall with Poster Viewing

       Sponsored by
4:20 Cell-Based and in vitro Protein Complex Analyses using Protein-Fragment Complementation Assays (PCA)
John K. Westwick, Ph.D., President and CEO, Odyssey Thera, Inc. 
To advance the field of protein interaction analysis and therapeutic development, technologies are required that are both high throughput and highly contextual. Technologies aimed at monitoring native cellular complexes are generally laborious low throughput, and therefore unsuitable for analysis of large chemical files. High throughput reductionist in vitro strategies, on the other hand, often fail to mirror cellular context and thus fail to identify active and safe therapeutic agents.

To address these challenges, we have developed live cell, protein complex-based high-content signal transduction assays using protein-fragment complementation (PCA). We will describe engineering and validation of assays for multiple targets from high profile as well as “un-drugable” target classes. These assays were used individually in drug screening campaigns to identify novel small molecules and nucleic acids (siRNAs, miRNAs) capable of modifying these interactions and pathways in living cells. We expanded these capabilities to create a large and diverse panel of signaling assays that are run in parallel arrays, enabling system-wide signaling analysis and definition of compound mechanisms, selectivity and safety. We also engineered an integrated platform comprised of semi-automated cell handling, automated liquid handling, high throughput automated microscopy, and the requisite automated image analysis, IT infrastructure and data mining capabilities to support analysis of large chemical files.

4:50 Moving in New Circles – Exploiting Macrocycles for Drug Discovery

Nick Terrett, Ph.D., CSO, Ensemble Therapeutics Corp.

5:20 Breakout Discussions:

Topic 1: Low Hanging Fruits: High Impact from Simple Computational Tools

Moderator: Woody Sherman, Ph.D., Vice President of Applications Science, Schrodinger

Topic 2: Possibilities and Challenges of Studying Protein-Protein Interactions under Physiological Conditions

Moderator: Alexander Shekhtman, Ph.D., Associate Professor, Chemistry, State University of New York at Albany

Topic 3: Predicting Protein-Protein Interactions – Problems and Tools

Moderator: Sandor Vajda, Ph.D., Professor, Biomedical Engineering and Chemistry, Boston University

Topic 4: Developing Small Molecule Modulators of PPI - Computational Aspects

Moderator: Gabriela Mustata, Ph.D., PharmacoInformatics Specialist, Computational and Sytems Biology, University of Pittsburgh

6:30 End of Day

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