7:00 am Morning Networking Coffee
7:50 am Chair’s Opening Remarks
Advancements in Targeted Protein Stabilization Showcasing the Therapeutic Potential of Induced Proximity
8:00 am Harnessing Deubiquitinases (DUBs) for Targeted Protein Stabilization (TPS) & Restoration of Protein Function
Synopsis
- Identifying therapeutically relevant proteins for targeted stabilization
- Profiling novel ligands for DUB recruitment
- Presenting novel insights into TPS and RESTORAC development
8:30 am Using Small Molecular Glues for Selective Stabilization of Clinically Beneficial 14-3-3 Protein Interfaces
Synopsis
- Identifying key 14-3-3 protein complexes that can be stabilized for therapeutic effect
- Studying the binding grooves that 14-3-3 interaction unveil for targeting through small molecules
- Hunting for natural and synthetic molecular glues that can stabilize clinically relevant 14-3-3 complexes
9:00 am Presenting Protein Rescue Targeting Chimeras (PRESTACs) for Targeted Protein Stabilization
Synopsis
- Leveraging the targeted stabilization of therapeutically relevant proteins which can be achieved by recruiting Deubiquitinases (DUBs) to deubiquitinate target proteins and prevent their degradation
- Exploring how heterobifunctional molecules, called Protein Rescue Targeting Chimeras (PRESTACs), can be generated by chemically linking a DUB ligand to a target protein ligand
- Understanding how Progenra has discovered and characterized novel small molecule DUB ligands which are used to design and synthesize PRESTACs to stabilize disease-relevant targets
- Learning strategies for discovering and characterizing novel DUB ligands using Progenra’s UbiProTM platform will be discussed
9:30 am Morning Break & Networking
10:00 am PANEL DISCUSSION: Tackling the Unique Challenges that Novel Proximity Approaches Face for Efficient Drug Development
Synopsis
Addressing the differences between targeted protein degradation and other modalities, along with the challenges that arise from this, such as:
- What are the benchmarking standards when creating new protein species to test the efficacy of your drugs?
- How to address the reversibility of post-translational modifications for sustained therapeutic effect?
- Increasing the bio-chemical and bio-physical understanding of new reactive protein species to drive specific pharmacological effects
From Post-Translational Modifications to Transcriptional Control: Uncovering Emerging Modalities Pushing the Frontiers of Induced Proximity
10:45 am PANEL DISCUSSION: Finding the Gaps – Discussing the Unmet Needs that Novel Modalities Are Filling to Push the Therapeutic Limits of Induced Proximity
Synopsis
- Evaluating hard-to-drug targets that novel approaches can unlock
- Bridging the gap between a clinically relevant target and a therapeutic modification
- How to design unbiased screens to find binders across the proteome
11:30 am Regulated Induced Proximity Targeting Chimeras: Using RIPTACs to Selectively Kill Cancer Cells
Synopsis
- Describing a novel “hold & kill” approach to selectively treat cancers
- Elucidating the mechanism of action of RIPTACs
- Accelerating the proof-of-concept gain for further novel RIPTAC therapies
12:00 pm Networking Lunch
1:00 pm Precision Control of Transcription Using Bio-orthogonal Chemical Epigenetic Modifiers
Synopsis
- Understanding how bio-orthogonal Chemical Epigenetic Modifiers allow for dose dependent gene activation
- Leveraging chemical induced proximity with small bifunctional molecules that bridge gene targeting systems with endogenous gene activators
- Exploring novel translational applications of this technology in human disease
1:30 pm Showcasing Chemically Induced Proximity & CRISPR Strategies to Regulate RNA Modifications
Synopsis
- Understanding the function and disease relevance of RNA modifications
- Leveraging an inducible CRISPR platform for m6A editing
- Engineering a split Cas13b system for RNA regulation
2:00 pm Inducing Dephosphorylation of Kinases by Inducing Proximity Between PP1 & AKT1 & EGFR (Virtual)
Synopsis
- Showcasing proof of concept for inducing proximity between a phosphatase (PP1) and kinases (AKT and EGFR) Elucidating the chemical strategy for heterobifunctionals that recruit phosphatases
- How to identify key targets that are solvable through phosphatase activity
2:30 pm Afternoon Break & Networking
3:00 pm Navigating the Interplay of Acetylation & Ubiquitination
Synopsis
- Understanding how acetylation of non-histone proteins has emerged as an important mechanism of regulation for the ubiquitin-proteasome system, particularly at the level of E3 ligase substrate recognition
- How to identify a subset of proteins with stability regulated at the level of post-translational acetylation
- Leveraging these acetylation sites that can be altered by induced proximity modalities for desired effects
3:30 pm Targeting Histone Acetylation & Key Structure-Function Relationships
Synopsis
- Dissecting the structural function of HAT containing protein
- Using induced proximity to change the core-regulatory circuitry network
- Studying proximity induced degradation impact on the protein complex in cancers
4:00 pm Examining Proof of Concept (PoC) Studies of Catalytic, Proximityinduced, Autophagy-dependent Degradation of Proteins & NonProtei
Synopsis
- Comparing and contrasting the ubiquitin-proteosome system vs autophagy-lysosome system
- Studying the PoC studies of proximity-induced, autophagy-dependent degradation
- Elucidating the potential of autophagy-based, targeted degradation