DAY ONE - Wednesday May 8, 2024

8:00 am Check-In & Morning Coffee

8:50 am Chair’s Opening Remarks

  • Daniel Scott Senior Scientist, St. Jude Children's Research Hospital

Identification & Validation of Novel E3 Ligases with Improved Specificity & Safety to Unlock Novel Drug Targets

9:00 am Discovery of Novel E3 Ligase Ligands for Targeted Protein Degradation

Synopsis

  • Identifying novel E3 ligase for targeted protein degradation – target selection based on tractability and activity
  • Evaluating E3 ligase activity before discovering chemical binders
  • Debating current limitations to find E3 ligands for targeted protein degradation

9:30 am Leveraging C-END E3 Ligases for PROTAC Development

  • Daniel Scott Senior Scientist, St. Jude Children's Research Hospital

Synopsis

  • Are Cullin-RING C-END substrate receptors viable candidates for PROTAC development?
  • Are ligands targeting C-END substrate receptors selective?
  • Can PROTACs overcome inherent E3 regulatory mechanisms?

10:00 am Gluing the Pieces Together, to Break it All Down – Harnessing Novel E3 Ligases for Molecular Glue Degraders

Synopsis

  • The field of TPD currently lacks rational chemical design principles for converting protein targeting ligands into molecular glues
  • Using known protein binders, we sought to identify transposable motifs which would convert these ligands into protein degraders
  • RNF126, a previously unliganded RING E3 ligase, was determined to be an amenable ligase mediating a multitude of neo-substrate recognition events, leading to the discovery that it could be harnessed in a protein complex and act as an effective ubiquitinating and degrading chaperone

10:30 am Morning Break & Speed Networking

Synopsis

Our speed networking is the ideal opportunity to get face-to-face time with many of the brightest minds working in the field & introduce yourself to the attendees that you would like to have more in-depth conversations with. Benchmark against industry leaders & establish meaningful business relationships to pursue for the rest of the conference & beyond.

Deconvoluting Cellular Biology to Understand Untapped E3 Ligases & Expose the Functional Relevance in Broader Disease Indications

11:30 am Exploiting the Cellular Biology & Localization of E3 Ligases to Elucidate their Utility for Targeted Therapeutics

Synopsis

  • Why must we address the cellular context of novel E3 ligases and how?
  • How to elucidate the regulatory mechanisms governing E3 ligases, including posttranslational modifications and interacting partners?

12:00 pm Proximity Biotinylation for Identification of Degraders & Molecular Glues

  • Dalia Barsyte-Lovejoy Principal Investigator & Professor, University of Toronto & Structural Genomics Consortium

Synopsis

  • Proximity biotinylation enables assessing the interactome of E3 ligase complexes
  • Compound based perturbations of interactome can identify new substrates and new E3s
  • Targeting dynamic ubiquitin signaling complexes

12:30 pm Employing In Vitro Ubiquitylation Assays to Streamline the Progression Towards Efficacious Degrader Drugs

Synopsis

  • What in vitro assays demonstrate high predictive value towards degrader drug efficacy?
  • How can this be optimized?
  • How to ensure the suite of in vitro assays are easily portable to various E3 ligases?
  • How to establish a correlation between ligase ubiquitylation efficiency in vitro and cellular neo-substrate degradation?

1:00 pm Networking Lunch Break

2:00 pm Roundtable Discussion: Addressing the Dynamic Behavior of E3 Ligases to Understand its Implications in Substrate Binding & Catalysis

Synopsis

  • How to understand the dynamic molecular movements of E3 ligases?
  • What advanced structural techniques can we deploy to capture this?
  • How do these dynamics impact the engagement of substrates?

3:00 pm Afternoon Networking Break

Enhancing Structural Profiling & the Characterization of Complex Formations to Inform the Progression of Druggable Ligases

4:00 pm Exploiting In-Solution Structural Dynamics for the Design of CRBN Ligands & Neo-Substrate Recruitment

  • Marcus Hartmann Group Leader, Max Planck Institute for Biology Tübingen & University of Tübingen

Synopsis

  • Guidelines to design ligands with high specificity for CRBN
  • Identification of DMSO-related artefacts in CRBN assays
  • Following ligand-induced folding and neo-substrate recruitment in solution

4:30 pm Structural Characterization of WDR5-VHL Ternary Complex Interfaces & their Implications on Degrading Efficiency

  • Andreas Kraemer Principal Investigator, Goethe University Frankfurt am Main & Structural Genomics Consortium

Synopsis

  • Can we improve PROTAC design based on ternary complexes crystal structures?
  • Is there a correlation between complex interfaces and degrading efficiency?
  • How do we track ternary complex formation in vitro and in cells?

5:00 pm Chair’s Closing Remarks & End of Conference Day One

  • Daniel Scott Senior Scientist, St. Jude Children's Research Hospital