8:00 am Check-In & Morning Coffee
8:50 am Chair’s Opening Remarks
Advancing Screening Technologies to Access Diverse Chemical Matter & Accelerate the Discovery of Stabilizing & Modulating Induced Proximity Therapies for Novel Targets
9:00 am Identifying MYC Interactome Modulators via Small Molecule Microarray Screening
Synopsis
- Using the Small Molecule Microarray platform to screen the MYC transcription factor complex in nuclear lysates of MYC-driven tumor cells
- Triaging hits through a series of assays for known MYC cofactors and interactors
- Identifying and characterizing a novel binder to the MYC cofactor WDR5 and a novel disruptor of the MYC:WDR5 interaction that led to MYC protein destabilization
9:30 am Non-Degrading Macrocyclic Type I Molecular Glues: Glue Libraries for Inhibiting PPI’s
Synopsis
- A platform for producing DEL and Array libraries for screening against hard to drug targets
- Principles for achieving cell permeability for BRo5 molecules with results
- Examples of the application of the platform to disease targets
10:00 am Utilization of Mass Spectrometry to Efficiently Identify & Validate DUB Recruiters & DUBTACs
Synopsis
- Utilizing chemoproteomics to identify allosteric covalent binders to DUBs – screening covalent compounds in cells and measuring competition between the compounds and the desthiobiotin iodoacetamide (DBIA) probe to identify DUBs that are covalently modified by the compounds
- High throughput screening of covalent compounds against recombinant DUBs/DUB domains to efficiently identify chemical starting points for recruiters
- Identifying a rational approach to identifying optimal DUBs for induced proximity based on the results of screening covalent compounds in cells and against the recombinant proteins
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.
Pioneering Platforms to Define the Framework for Rationally Designing Safe & Efficient Induced Proximity Drugs with Novel Mechanisms of Action
11:30 am Discovery of FKBP Molecular Glues Using DEL & Diverse Protein Domains
Synopsis
- FKBP-molecular glues (FK506 and rapamycin) have been widely used clinically, but our understanding of the breadth of novel FKBP molecular glues/targets has yet to fully revealed
- Identifying novel FKBP molecular glues/targets by screening multi-million member FKBP-ligand scaffold DNA-encoded libraries against ~100 purified protein targets representing a diverse collection of domains/structural elements
- Revealing selected examples of FKBP molecular glues and discussing implications of using this platform in general for molecular glue discovery
12:00 pm Round Table: Tackling the Rationale Design of Molecular Glues with Advancing Platforms to Generate High Efficacy Clinical Candidates
Synopsis
- How can we learn from and leverage the platforms used to develop heterobifunctional small molecules for molecular glues?
- What are the key design principles of molecular glues that needed to be considered when developing discovery platforms?
- What advances in technology, toolbox or data will facilitate the rational design of molecular glues? How can we acquire these?
12:30 pm Magnet Biomedicine’s TrueGlue Platform: The Next Frontier in Precision Localization
Synopsis
- Magnet Biomedicine is advancing precision medicines through rational selection of protein pairs and systematic design of monovalent molecular glues
- Combining the benefits of small molecule drugs with the high specificity of antibodies, TrueGlues offer the potential to address the most challenging targets in a tissue localized manner to address a range of indications with high unmet need, including cardiovascular disease, cancer, and immune disorders
1:00 pm Networking Lunch Break
Understanding Chemistry & Biology Fundamentals to Inform & De-Risk Novel Emerging Induced Proximity Approaches in New Disease Paradigms
2:00 pm Discovery Proteomics for Investigating Interactomes
Synopsis
- Understanding protein-protein interactions to identify new mechanisms for drug discovery and development, particularly for difficult targets where inhibition alone is not sufficient to carry out a therapeutic effect
- Showcasing a “twist” on traditional proximity ligation methods that can be conducive to identifying new modes of actions through complexes and transient interactions
- Leveraging our proximity ligation assay to identify changes in complexes and transient transactions which can be harnessed in hit discovery campaigns
2:30 pm Round Table: Deliberating the Biological Synergy of Un-Endogenous Protein Partners when Co-opted as Targets for Induced Proximity to Mitigate Off Target Toxicity
Synopsis
- What criteria are considered when choosing un-endogenous protein partners for induced proximity?
- How to lean into the synergy of nominated protein pairs when considering biological responses?
- How to leverage the tissue selectivity of protein partners to mitigate off target toxicity and improve safety?
3:00 pm Afternoon Networking Break
4:00 pm Improving the Potency of Nature’s Molecular Glues by Leveraging Synthetic Biology to Drug Protein-Protein Interfaces
Synopsis
- How to leverage synthetic biology to enhance the potency and/or properties of small molecules?
- What are the key synthetic biology technologies and techniques to design heterobifunctional compounds to interrogate the pharmacology of protein-protein interfaces?
- What challenges are associated with leveraging synthetic biology? How to overcome these?
4:30 pm Progressing Induced Proximity Approaches to Specifically Mediate Chromatin Regulation & Expand the Repertoire of Clinically Relevant Disease Targets
Synopsis
- What are the key chromatin-associated proteins that can be targeted using induced proximity strategies?
- How to tailor heterobifunctionals to selectively activate or repress specific genes by modulating chromatin accessibility?
- How to elucidate the molecular interactions between the drug and chromatin components?
- Can induced proximity drugs be engineered for cell-type-specific chromatin regulation?