8:30 am Registration & Morning Coffee

9:20 am Chair’s Opening Remarks

Uncovering Screening Technologies to Identify Molecular Glue Degraders

9:30 am Photochemicalbiology for the Identification of Basal E3:POI Interactome

  • Joel Austin Senior VP of Platform Technology Development, Seed Therapeutics

Synopsis

• Known molecular glues for TPD increase the avidity of a weak basal interaction between an E3 Ligase and a Protein of Interest
• A broadly robust technology to identifying these weakly productive basal interactions in a cellular context does not exist. Thus the discovery of molecular glues has historically been serendipitous
• Seed has advanced the area of photochemicalbiology and has demonstrated local interactome mapping to identify cellularly relevant weak basal interaction between an E3 Ligase and a Protein of Interest

10:00 am Screening Rationally Designed MGD Libraries to Unravel Degradable Proteins

  • Yong Cang CSO & Co-Founder, Degron Therapeutics

Synopsis

  • MGDs bind E3 ubiquitin ligases and create neomorphic surface for novel PPI
  • MGD libraries are rationally designed with chemical diversity and drug-like properties.
  • Phenotypic, proteomic and reporter screening strategies are used to identify degradable proteins by the library compounds

10:30 am Luminescence Technologies to Enable Discovery & Optimization of Effective Targeted Protein Degraders

Synopsis

  • A comprehensive suite of luminescence-based assays for degrader screening, characterization, and optimization
  • Screening workflow considerations for PROTAC and molecular glue degraders
  • Importance of cellular kinetics for optimizing degrader mechanism and efficacy

11:00am Morning Break & Speed Networking

Synopsis

As the TPD community is reunited, this valuable session will ensure you can connect with your peers in the room to make new and lasting connections. Also, don’t forget to enjoy some refreshments before we come back after the break!

12:00 pm High Throughput Strategies to Prospectively Identify Molecular Degraders

  • Toren Finkel Professor & Director of the Aging Institute, University of Pittsburgh School of Medicine

Synopsis

• Prospective Identification of Molecular Degraders has been challenging
• We have devised a HTS platform that can identify ligand binders to a diverse array of challenging targets
• A subset of identified small molecule ligand binders induce proteasomalmediated target degradation

12:30 pm NanoBRET Technology as a Tool for MGD Identification & Validation

Synopsis

• NanoBRET in the screening cascade
• NanoBRET as a complementary assay for Turbo ID and HTRF
• Miniaturization of NanoBRET for library screening

1:00 pm Mastermind Discussion: How to Design & Optimize the Screening Strategy Specifically for Molecular Glues

  • Toren Finkel Professor & Director of the Aging Institute, University of Pittsburgh School of Medicine
  • Yong Cang CSO & Co-Founder, Degron Therapeutics

Synopsis

• What are the different strategies for the rational discovery of glues?
• Assessing & comparing DEL, TR-FRET assays, FP-based screening and positive selection screening technologies to identify glues
• Screening funnels for taking target agnostic approach

1:30 pm Networking Lunch

Revealing Innovation in Proteomics to Fast-Track Hit Finding

2:30 pm Uncovering Proteomic Approaches in Drug Discovery

  • Kirti Sharma Senior Director - Proteomics, Kymera Therapeutics

Synopsis

• How to successfully set up proteomic studies to find new starting points
• Utilizing proteomic studies to decipher when proteins are downregulated and how this effects the whole pathway
• How can this toolbox be optimized to screen for disease related proteins?

3:00 pm Global Mass Spec Proteomic Profiling to Inform TPD Discovery

  • Harris Bell-Temin Associate Director, Discovery Proteomic Platforms, Janssen Pharmaceutical Companies of Johnson & Johnson

Synopsis

• Discuss the paradigm shift in rapid, deep, and quantitative proteomics enabled by recent improvements to instrumentation and computational platforms
• Explore how proteomics can inform not only chemical matter screens but target and E3 ligase selection
• Show how including mass spec proteomics can speed chemical matter
optimization and improve translatability of screening data

Remote Presentation

3:30 pm Afternoon Break & Networking

Optimizing Cell-Based & Biophysical Assays to Determine the Mechanism of Action

4:00 pm Assay Development Towards the Optimization of Effective Degraders

Synopsis

• Targeted protein degradation (TPD) is an emerging novel therapeutic modality with the potential to tackle traditionally difficult to target (undruggable) disease-causing proteins
• Highly efficacious degraders (PROTAC) induce rapid and selective degradation of the POI with high potency (DC50) and high maximal degradation (Dmax). To optimize such parameters a sensitive bioluminescence protein quantitation system for the POI was established using Promega’s Nano-Glo HiBiT Detection System
• Further analysis revealed differential degradation of isoforms and the need for further development of cellular degradation assay approaches to fully understand these difference

4:30 pm The Biophysical Basis of Indisulam-Mediated Recruitment of RBM39 to the DCAF15-DDB1-DDA1 E3 Ligase Complex

Synopsis

• Indisulam was discovered in a phenotypic screen and assumed to work as an anti-proliferative agent as a carbonic anhydrase inhibitor and disruption of proton homeostasis
• Subsequent studies and assays suggested that indisulam was a molecular glue which reprograms the DCAF15 E3 ligase to degrade a class of RNA-binding motifs
• Biophysical assays and structural studies confirm this hypothesis and further define the nature of this molecular glue

5:00 pm Round Table Discussion: Optimizing in-vitro Assays to Better Inform in-vivo Studies

  • Oscar Huang Principal Scientist, Biochemistry & Biophysics, Bristol Myers Squibb

Synopsis

• What is the best approach to measure workflow in in-vitro testing funnel to identify the best molecules for in-vivo?
• How to optimize in-vitro assays to guide bioavailability
• What assays are most predictive when you move in-vivo?

5:30 pm Chair’s Closing Remarks & End of Conference Day One