**All times in EDT**

8:30 am Chair’s Opening Remarks

Harnessing Chemical Biology for Discovery & Development of Ubiquitin Ligases with Therapeutic Value

9:00 am Activation of the RING E3 Anaphase-Promoting Complex/ Cyclosome (APC/C)

Synopsis

  • Exploring the APC/C as master regulator of the cell cycle
  • Discuss the benefits of APC/C ubiquitination activity as tightly regulated and dynamic
  • Outline a mechanism to stimulate the APC/C and the implications for other RING E3s and the cell cycle

9:25 am Molecular Mechanisms of Small Molecule-mediated NEDD4 Targeting

  • Simona Polo Professor, IFOM, the FIRC Institute for Molecular Oncology & DIPO, Department of Oncology and Hemato-oncology, University of Milan

Synopsis

  • Reviewing the C2-WW-HECT E3s (also named NEDD4 family) as they appear to be promising targets for drug discovery. Their activity is tightly controlled through an auto-inhibitory interaction of C2 with HECT domain that can be released upon phosphorylation
  • Exploring how they build K63-specific chains using a sequential addition mechanism and utilize a ubiquitin exosite required for enzyme processivity
  • Discussing how we generated small molecules capable of selectively inhibiting NEDD4 polyubiquitylation without affecting its monoubiquitylation activity. These molecules are currently testing towards tumours of neuroendocrine origin

9:50 am Drugging Transcription Factors and Kinases by Preventing E3- Dependent Degradation

  • Toren Finkel Chief Scientific Officer, Generian & Professor of Medicine and Director, Aging Institute, University of Pittsburgh/UPMC

Synopsis

• Building on our understanding of the role of aging in disease to discover new therapies
• Leveraging E3 biology to enhance the beneficial effects of therapeutic proteins with short half-lives
• Outlining generian’s two IND programs and how they address previously undruggable validated therapeutic targets, both with an opportunity for clinical proof of mechanism in rare conditions, with expansion into common disorders

10:15 am Live Panel Q&A – Ask the Speakers Your Burning Questions!

  • Ingo Hartung Director Medicinal Chemistry , Merck KGaA
  • Simona Polo Professor, IFOM, the FIRC Institute for Molecular Oncology & DIPO, Department of Oncology and Hemato-oncology, University of Milan
  • Toren Finkel Chief Scientific Officer, Generian & Professor of Medicine and Director, Aging Institute, University of Pittsburgh/UPMC

10:30 am

Morning Break & Speed Networking

Exploring Rational Design & Future Potential of Harnessing E3 Ligases for Therapeutic Application

11:30 am Targeting the Ubiquitin Ligase Activity of MDM2

  • Danny Huang Senior Group Leader & Professor of Cancer Structural Biology, University of Glasgow

Synopsis

  • Exploring the inactivation of MDM2’s ubiquitin ligase activity stabilizes p53 but can still limits p53 activity
  • Discussing ligase inactive MDM2 mouse restrains p53 activity for normal growth but enhances p53 activity upon stresses
  • Sharing insights into targeting the catalytic activity of MDM2

11:55 am What Makes Two Proteins Stick: Dissecting E3’s Contribution to Molecular Glue Action

  • Nicolas Thomä Senior Group Leader, Friedrich Miescher Institute for Biomedical Research in Basel

Synopsis

  • Protein-protein interactions can be induced by slight modification of the surface chemistry of the target!
  • How can this be routinely triggered by small molecules?
  • Or is this likely already an intrinsic property of many drugs?

12:20 pm Accelerate Mass Spectrometry Protein Sample Preparation and Quantification

  • Earl Walker Senior Technical Product Specialist Mass Spectrometry Proteomics/Biomarker Discovery and Validated Immunoassays Workflows,
  • Vatsav Raman Technical Product Specialist, Flow Cytometry, Thermo Fisher Scientific

Synopsis

  • Discovery and targeted proteomics
  • Options for high throughput profiling
  • Custom peptides for therapeutics & vaccine development

12:35 pm Live Panel Q&A – Ask the Speakers Your Burning Questions!

  • Ingo Hartung Director Medicinal Chemistry , Merck KGaA
  • Danny Huang Senior Group Leader & Professor of Cancer Structural Biology, University of Glasgow
  • Nicolas Thomä Senior Group Leader, Friedrich Miescher Institute for Biomedical Research in Basel

12:50 pm

Lunch Break & Networking

1:50 pm PANEL DISCUSSION: Exploring the Therapeutic Value of Targeting E3 Ubiquitin Ligases

  • Pengyu Yang Associate Director, Plexium
  • Xiaoran Han Director of Discovery Medicine, Cullgen Inc
  • Claudio Thoma Senior Principal Scientist, Novartis Institutes for Biomed Research, Inc
  • Jennifer Venable Senior Scientific Director, The Janssen Pharmaceutical Companies of Johnson & Johnson
  • Rick Davies Associate Director, AstraZeneca Pharmaceuticals

Synopsis

Using advanced techniques, our understanding of E3 ligases complex structure has improved, identifying bindable pockets on E3 ubiquitin ligases. Similarly, innovative screening methods have identified ligase binders. With this, how can we begin thinking about these interactions as a starting point for viable

  • Examining the industry standpoint on E3 targeted therapeutics and the overarching strategy to consider targeting E3’s as a viable therapeutic
  • What are the next steps to enhance small molecule targeting E3 therapies into the clinic and beyond?
  • As tissue-selectivity becomes increasingly important, what are the difficulties of selectively targeting E3’s in tumor cells and tissue types of interest?
  • What breakthroughs and milestones on the horizon?

2:50 pm Poster Session – Present, Learn & Collaborate

Synopsis

As the viability of harnessing E3’s for therapeutic application becomes increasingly evident, it is more important than ever to collaborate and learn with your peers as we continue to advance ligase targeted therapies through discovery and development.

Join our dedicated session to share your latest data and have a first look about what your peers are working on!

3:30 pm Structure Based Design of E3 Targeted Protein Degraders

Synopsis

  • Discussing the viability and mechanisms of molecular glues
  • Outlining optimal structure-based drug design of E3 protein degraders
  • How you can leverage the structural insight of E3 ligases for an effective degrader mechanism

3:55 pm CRL E3 Ligases: From Catalytic Mechanisms, Assembly to Targeted Protein Degradation

Synopsis

  • Can we target RING-type E3 ligases?
  • Why are CRL E3 ligases particularly suitable for targeted protein degradation?
  • How can we hijack CRL to target other proteins?

4:20 pm From Screening to Targeted Degradation: Strategies for the Discovery and Optimization of Small Molecule Ligands for PCSK9

Synopsis

  • Identification and optimization of a Small Molecule Ligand for PCSK9
  • Demonstration of binding of that ligand in complex mixtures
  • Development of PCSK9 degrader based on that ligand

4:45 pm Live Panel Q&A – Ask the Speakers Your Burning Questions!

5:00 pm Chair’s Closing Remarks & End of Ligase Targeting Drug Development