CONFERENCE DAY ONE

7:50 am Check-In & Light Breakfast

8:50 am Chair’s Opening Remarks

Streamlining Screening Strategies to Identify Novel & Rational-Based Molecular Glue Drug Discovery

9:00 am Using Screening Assays & Predictive Data from GlueXplorer to Drive Forward Rational Discovery of Molecular Glues

  • Julia Dou Director of Protein Chemistry, Degron Therapeutics

Synopsis

  • Searching potential compounds for targets based on proximity mass spectrometry to get a molecular glue hit
  • How to use mass spectrometry data and in silico predictions to rationally discover a molecular glue
  • Accelerating screening by combining AI predictions with experimental data to explore specific chemical space

New Data

9:30 am Supercharging Discovery & Characterization of Molecular Glues Using High-Purity FRET-Active E2-Ubiquitin Conjugates

  • Dmitri Ivanov Associate Professor Biochemistry & Structural Biology, University of Texas Health San Antonio

Synopsis

  • Accurate measurement of ubiquitin transfer rates offers unprecedented insight into molecular glue-induced proximity of ligases and substrate proteins
  • Real-time, high-sensitivity fluorescent assays offer a path for high-throughput discovery and characterization of molecular glues
  • How gluey is your glue? Accurate measurement of binding affinities at all intermolecular interfaces illuminates energetics or ternary complex assembly

New Data

10:00 am Morning Break & Speed Networking

Synopsis

This networking session is your opportunity to get face-to-face with many of the brightest minds working in the molecular glue field and establish meaningful business relationships to pursue for the rest of the conference

Identifying Novel Molecular Glues Through Improved Screening Assays & Proteomic Tools to Identify Hits & Optimize Compound Binding

11:00 am Implementing Medicinal Chemistry & Proteomic Studies to Identify Novel Molecular Glues & Neo-Substrates

  • Meizhong Jin Senior Director - Oncology Chemistry, AstraZeneca

Synopsis

  • Diving into medicinal chemistry efforts to optimize compound binding and other properties
  • Employing proteomic profiling to understand the molecular glue degrader potential
  • Applying a network-based approach to prioritize novel neo-substrates from large-scale omics data

11:30 am Turbocharging Molecular Glue Design by Starting with Protein of Interest to Develop More Effective Glues

Synopsis

  • Devising screening libraries based on the chemical space of known binders to the protein of interest
  • Deconvoluting the novel ligases recruited in complex in the cellular context of protein of interest and molecular glue
  • How to develop a target centric screen to identify potential molecular glues

New Data

12:00 pm Deep-Diving into Unbiased Screening Strategies to Identify Novel Molecular Glues & Deconvolute Their Mechanism

Synopsis

  • Outline of how WIZ degrader was identified through a small-scale unbiased screen
  • How to improve strategy for unbiased screening including improving assay design, in built controls and mechanism of action deconvolution strategy
  • Demonstrating the mechanism of action deconvolution detailing methods used for a literature compound with currently unknown mechanism of action

New Data

12:15 pm Networking Lunch

Discovering Novel Small Molecule Glues by Harnessing Novel Ligases & Optimizing Binders

1:15 pm Exploring Chemical Space of Molecular Glues to Identify Suitable Ligands for Novel E3 Ligases

  • Bin Liu CEO, HB Therapeutics, Inc.

Synopsis

  • Discovering novel small molecule glues for targeted protein degradation of SUMO1
  • Utilizing the E3 ligase complex structure for structure-based glue degrader design
  • SUMO1 degradation MOA and SAR highlight for potency and properties

New Data

New Company

1:45 pm Fireside Chat:Diving into Methods Used to Discover Novel Ligases & Molecular Glues

Synopsis

  • How are novel and effective ligases being discovered?
  • What are the potential endogenous interactions that can be targeted and exploited?
  • Can libraries of ligases be built that have increased activity with molecular glues?

2:15 pm Harnessing & Optimizing Ligases Binders as Molecular Glues that are Active with E3 Ligases Beyond Cereblon

Synopsis

  • How to approach testing and establishing the glue activities of novel E3 ligases
  • Repurposing PROTAC binder ligands as molecular glues for ligases beyond Cereblon
  • How to characterize ligase binders and identify targets that can be degraded

New Data

2:45 pm Afternoon Networking Break

Drugging Undruggable Targets & Hard to Treat Diseases with Novel Molecular Glues

3:15 pm Discovering Molecular Glue by High-Throughput Neomorphic Remodeling of Effector Proteins

  • Jia Liu Principal Scientist, PhoreMost

Synopsis

  • Developing a new protein-editing approach to molecular glue discovery
  • Exploring molecular glues for undruggable targets such as STAT3
  • Synthesizing computation tools with biology to discover degrader glues

New Company

3:45 pm Panel Discussion: Spearheading Structure-Based Rational Design to Develop More Effective Molecular Glues

Synopsis

  • What are the structural considerations between ligases, target proteins and molecular glues in rational design?
  • How to overcome the difficulties in turning protein models from crystal structures to dynamic models
  • What information do the different computational models give about the ternary complexes and how can this be leveraged in molecular glue design?

New Companies

4:30 pm Discovering a Molecular Glue Active in the Parkin Ligase & PINK1 Kinase Signaling Pathway & its Role in Neurodegeneration & Aging

Synopsis

  • Targeting Parkinson’s Disease and Alzheimer’s Disease to correct mis-folded proteins or remove aggregated proteins
  • Activating PINK1 kinase:Parkin using a molecular glue to phosphorylated ubiquitin to rejuvenate health
  • Developing a molecular glue for parkin ubiquitin ligase that induces mitophagy, mitobiogenesis and improves neuronal health

New Company

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