Archived Content

Friday, May 23, 2014


7:30 am Chairperson's Remarks

ChaguturuRathnamRathnam Chaguturu, Ph.D., Founder & CEO, iDDPartners; Senior Director, Discovery Sciences, SRI International

7:40 Continental Breakfast and Breakout Discussions

Enjoy breakfast while joining a discussion group. These are moderated discussions with brainstorming and interactive problem solving, allowing conference participants from diverse backgrounds to exchange ideas, experiences, and develop future collaborations around a focused topic.

Table 1: Collaborative Innovation Drives Chemical Biology 

Discussion Points Include:

  • Governmental Initiatives Accelerate Pre-Competitive Collaboration
  • Nonprofits Drive Bench to Bedside Innovation
  • Intellectual Property and Technology Transfer
  • Academic Screening Centers Come of Age: Strategies to Collaborate with Industry to De-Risk Initiatives in Novel Biology

Table 2: Emerging Game-Changing Technologies in Chemical Biology Rapidly Advancing Target Identification and Validation 

Discussion Points Include:

  • Usefulness of Repurposed Drugs as Novel Probes for New Targets
  • RNAi Screening Platforms: Pitfalls and Promise
  • Relevant Small Animal Models (Rodents, C.elegans, Zebrafish)
  • Target-Based vs. Phenotypic Drug Discovery: Pros and Cons, or Complementary

Table 3: Chemical Strategies to Expand Availability of Small-Molecules for New Biological Targets 

Discussion Points Include:

  • Strategies for Chemical Library Refinement to Improve Drug Lead Finding
  • Open Resources for Chemoinformatics to Help Academic Researchers
  • Renaissance in Pharmacognosy: Time to Revisit
  • Scientific Misconduct and the Problem of Irreproducibility

Chemical Tools and Strategies to Expand Pharmacological Modulation of Biological Processes 

8:35 Chairperson’s Remarks

Iván Cornella-Taracido, Ph.D., Head, Chemical Biology; Associate Director, Discovery Sciences Chemistry Innovation Centre, AstraZeneca

8:45 KEYNOTE PRESENTATION: Covalent Inhibitors of Oncogenic Signaling Pathways

Nathanael GrayNathanael Gray, Ph.D., Professor, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School; Professor, Cancer Biology, Dana-Farber Cancer Institute

There has recently been a resurgence of interest in covalent inhibitors. This lecture will discuss our efforts to develop efficient chemical approaches to generate and characterize covalent inhibitors of oncogenic kinases and of KRAS.

9:30 Chemical Proteomic Strategies to Investigate Reactive Cysteines

WeerapanaEranthieEranthie Weerapana, Ph.D., Assistant Professor, Chemistry, Boston College

We have applied chemical proteomics to identify and characterize functional cysteines in the human proteome. By combining small-molecule probe synthesis with mass spectrometry-based proteomics, we have identified reactive and functional cysteines that can be targeted for covalent inhibitor development. Our small-molecule probes act as pharmacological modulators of diverse protein activities.

10:00 Selected Poster Presentation: Strategies to Target Protein-Protein Interactions

Chiara Valenzano, Ph.D., Principal Scientist, UCB Celltech

10:15 Coffee Break in the Exhibit Hall with Poster Viewing

11:00 Diversity-Oriented Synthesis for Oncology Drug Discovery

LisaMarcaurelleLisa Marcaurelle, Ph.D., Vice President, Discovery Chemistry, H3 Biomedicine

H3 Biomedicine’s approach to oncology drug discovery leverages the vast amount of available cancer genomics data to identify novel molecular targets. This genomics-based approach is coupled with the creation of a unique compound collection with the potential to modulate a broad range of oncology targets. Libraries of sp3-rich small molecules containing one or more stereogenic centers have been assembled using the most recent developments in synthetic organic chemistry facilitated by parallel synthesis techniques. Library design is inspired by the molecular architecture of natural products and enabled by cheminformatics to yield compounds with maximal diversity and optimal physicochemical properties. To date over 15,000 compounds have been produced representing >100 distinct synthetic pathways. An overview of this work will be presented.

11:30 Natural Product-Based Strategies in Diversity-Oriented Synthesis

TanDerekDerek Tan, Ph.D., Member and Laboratory Head, Molecular Pharmacology & Chemistry Program, Sloan–Kettering Institute for Cancer Research, Memorial Sloan–Kettering Cancer Center

Advances in genomic technologies and molecular cell biology have revealed myriad new biological targets that are implicated in human diseases. However, our ability to translate these discoveries into new therapeutics is severely limited by the fact that existing small-molecule drugs address only a very small subset of ≈200 protein targets encoded in the human genome (≈1%). To address this critical problem, our laboratory is developing discovery libraries based on privileged structural motifs from natural products, which have a demonstrated ability to bind diverse biological targets. We develop new chemical methodologies to provide efficient and flexible access to these molecules, with current targets including spiroketals, macrocycles, and medium rings.

12:00 pm Luncheon Presentation (Sponsor Opportunity Available) or Enjoy Lunch on Your Own

Technological Advances enabling target validation 

12:55 Chairperson’s Remarks

Brent J. Passer, Ph.D., Director, Business Development, Hybrigenics Corp.

1:00 Paradigm Shift in Hit Identification and Lead Optimization

LitaoZhangLitao Zhang, Ph.D., Vice President, Leads Discovery & Optimization, Bristol-Myers Squibb

This presentation will outline critical roles of hit identification and lead optimization for target validation. Technology innovation has been and will continuously guide our ways to select right targets and deliver right therapeutic agents. Future trends in hit ID and lead optimization will center around complex biology, systematic approaches and chemical biology.

1:30 Multiplexed, Proteome-Wide Protein Expression Profiling to Explore Biological Function and Response

StevenGygiSteven P. Gygi, Ph.D., Professor, Cell Biology, Harvard Medical School

Mass spectrometry (MS) is a powerful measurement tool in biology. Using MS-based Proteomics, up to 10 samples can be simultaneously profiled for protein expression or posttranslational modification differences. This lecture will highlight i) the rationale for proteome-wide measurements, ii) the current status of multiplexing, and iii) future needs in the field. Examples of global expression profiling in colorectal cancer cell lines will be described.

2:00 Superbright Fluorophore-Tetrazine Turn On Probes for Bioorthogonal Imaging

JonathonCarlsonJonathan Carlson, M.D., Ph.D., Instructor, Medicine, MGH Cancer Center; Center for Systems Biology, Massachusetts General Hospital

In recent work we have developed fluorescent turn-on probes that exploit through-bond energy transfer (TBET) to achieve >1500-fold signal amplification upon bioorthogonal activation. These tetrazine-fluorophore derivatives are exceptionally quenched (non-fluorescent) until their characteristically fast, catalyst-free reaction with transcyclooctenol (TCO). This presentation will describe our progress in developing “clickdyes” that display excellent performance in real time, no-rinse imaging of TCO-labeled targets in vitro and in vivo.

2:30 Clickable Probes for Target ID, Mechanism of Action Studies, and Imaging: Case Study Using Clickable g-Secretase Photoaffinity Probes

DougJohnsonDoug Johnson, Ph.D., Associate Research Fellow, Neuroscience, Medicinal Chemistry, Pfizer

This presentation will describe how we have used clickable photoaffinity probes to investigate the mechanism of action studies of g-secretase inhibitors (GSIs) and modulators (GSMs), potential therapeutic agents for Alzheimer’s Disease (AD). Presenilin-1 N-terminal fragment (PS1-NTF) was identified as the protein target for GSMs and GSIs, however our data demonstrates that they bind to distinct sites. Furthermore, these clickable photoprobes enabled target engagement to be determined in live cortical neurons. Lastly, we developed a platform to image Cu-free clickable probes using the HaloTag protein as a model system in different subcellular compartments. This technology will be applied to image active g-secretase using Cu-free clickable GSI photoprobes.

3:00 KEYNOTE PRESENTATION: Genome-Wide Spatial Localization of Small Molecules

JamesBradnerJames E. Bradner, M.D., Assistant Professor, Department of Medicine, Harvard Medical School and Investigator, Department of Medical Oncology, Dana-Farber Cancer Institute



3:45 End of Conference

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