Explore the Agenda
8:00 am Check In & Refreshments
8:50 am Chair’s Opening Remarks
Deciphering the Molecular Basis of Induced Proximity to Enable Predictive & Mechanism-Guided Drug Discovery
9:00 am Principles Underlying Induced Proximity Drugs: Lessons from Early Development to the Present
- Introducing the core principles that underpin induced proximity therapies
- Highlighting key lessons from early approaches through to current developments
- Evaluating the evolving landscape of TPD and induced proximity
9:30 am αC-Helix–Proximal Allostery as a Platform for Selective Kinase Modulation & Complex Degradation
- Introduce a scalable structure-guided platform that combines SuFEx-based high-throughput medicinal chemistry and direct-to-biology screening to systematically discover aC-helix–proximal allosteric pockets across kinases
- Show how aC-helix–proximal engagement yields signaling-state-selective BRAF inhibitors that preferentially target RAF dimers and suppress dimerdependent MAPK signaling
- Demonstrate that the same strategy can generate CDK8/CDK19 modulators that destabilize CDK8/CDK19–Cyclin C complexes and trigger proteasomedependent degradation without requiring bifunctional degrader architectures
10:00 am Methylarginine Targeting Chimeras for Lysosomal Degradation of Intracellular Proteins
- Methylarginine degrons are a widespread signal for intracellular protein delivery to lysosomes
- MrTAC is a first-in-class lysosomal degrader
- Methyl-driven lysosomal proteolysis expands the scope of current proximity inducing modalities to new families of undruggable targe
10:30 am Morning Break & Networking Time
Discovering & Engineering Next-Generation Induced Proximity Systems to Leverage Novel Ligases & Accelerate Therapeutic Innovation
11:30 am Discovery of a Potent & Selective Molecular Glue Degrader of PPIL4 Active in Pediatric Acute Leukemia & Medulloblastoma
- Phenotypic screening of a CRBN based molecular glue library against pediatric cancer cell lines identified a potent cytotoxic compound (SJ42872)
- PPIL4 was identified as a novel neosubstrate using proteomics profiling
- In-vivo studies of SJ42872 in B-ALL and Medulloblastoma cells showed reduced tumor burden and increased survival in mouse models
12:00 pm Direct-to-Biology Discovery of Potent FBXO22 Homo-PROTACs
- We used a direct-to-biology approach to rapidly interrogate FBXO22-mediated degradation of 4 distinct targets (BRD4, BTK, CRBN and VHL), as well as the degradation of FBXO22 itself by 3 different E3 ligases
- Parallel synthesis of 175 candidate PROTACs containing primary alkylamine FBXO22 warheads, followed by direct testing of crude reaction products in cellular HiBiT assays, accelerated the discovery of highly potent and novel FBXO22 homo-PROTACs that induce self-degradation, as well as CRBN- and VHL-mediated degraders of FBXO22
- We show that FBXO22 homo-PROTACs induce ternary complex formation and the degradation in a proteasome dependent manner, supporting the selfdegradation mechanism
12:30 pm Lunch Break & Networking Time
Expanding Induced Proximity Modalities Beyond Degradation to Greater Leverage Biological Pathways & Broaden Therapeutic Options
1:30 pm Induced Proximity Tools for Discovery Biology
- Induced Proximity has a multitude of potential applications for drug discovery
- Post-translational modifications (PTMs) dominate cell signalling and are often mis-regulated in disease
- Chemical biology technologies enable the study of PTMs and testing of hypotheses, prior to therapeutic development
2:00 pm Enhancing Inhibition via Chemically Induced Proximity: A RIPTAC Targeting BCL6 & BET Proteins
- BCL6-directed BET inhibition: RIPTAC induces cooperative BCL6:BRD4 ternary complex formation, enhancing BET inhibition selectively in BCL6-high cancer cells
- Comparative mechanistic characterization of RIPTAC and TCIP: Structural and biophysical studies reveal that linker composition and BET warhead identity drive distinct ternary complex geometries and cooperativity profiles, providing a framework for understanding how bivalent molecule design shapes induced proximity pharmacology
- BCL6-mediated sequestration of BET proteins drives cytotoxicity: RNA-seq and BCL6-DNA binding mutant experiments show that cytotoxicity stems from enhanced BET inhibition, not transcriptional rewiring, suggesting the RIPTAC platform is broadly applicable to any disease context characterized by differential expression of a targetable protein
2:30 pm Panel Discussion: Shaping the Future of Induced Proximity Research to Drive Innovative Discovery & Support the Development of Pipeline-Ready Candidates
- Outlining recent advancements and breakthroughs defining the induced proximity field
- Creating a pathway for future research and innovation to enable the early development of future clinical candidates
- Highlighting the importance of industry and academia collaboration to enhance patient outcomes
3:00 pm Afternoon Break & Networking Time
Applying Next-Generation Technologies & Screening Platforms to Drive Innovation & Discovery Across Induced Proximity Mechanisms
3:45 pm GlueFinder: A Data-Driven Framework for the Rational Discovery of Molecular Glues
- GlueFinder enables rational molecular glue discovery: GlueFinder systematically mines protein structures to identify ligandable pockets near protein– protein interfaces that can stabilize ternary complexes between therapeutic targets and E3 ubiquitin ligases
- Broad applicability to major oncogenic targets: Applied to EGFR, HER2, and KRAS, GlueFinder predicted candidate molecular glues capable of recruiting 24, 111, and 148 distinct E3 ligases, respectively, substantially expanding the range of potential degradation strategies
- Transforms targeted protein degradation design: By decoupling glue discovery from traditional degrader scaffolds and dependence on specific ligases such as VHL and Cereblon, GlueFinder provides a general computational framework for expanding the druggable proteome
4:15 pm Diverse Mechanisms of Small Molecule Induced Protein Degradation
- Scalable reporter and screening platforms for systematic analysis of targeted protein degradation
- Defining CRBN substrate recognition rules to expand target discovery and guide rational degrader design
- Mapping mechanisms of degradation induced by small molecules through pooled CRISPR, flow cytometry, and quantitative reporter assays