Conference Day One
**All times in EDT**
8:30 am Registration & Chair’s Opening Remarks
Optimizing Discovery, Selection & Validation of E3 Ubiquitin Ligases
9:00 am Reimagining Druggability Using Chemoproteomic Platform
Synopsis
- Using chemoproteomic platforms to expand the scope of targeted protein degradation
- Using chemoproteomic platforms to develop next-generation induced proximity-based therapeutic modalities
9:25 am Drugging Tissue selective E3 ligases
9:50 am Arvinas’ PROTAC® Discovery Engine: Selecting & Employing E3s for PROTACs
Synopsis
- Overview of Arvinas’ PROTAC portfolio
- Overview of Arvinas’ PROTAC Discovery Engine platform
- Employing E3 ligases at Arvinas
10:15 am A Best In-Class Method to Quantify Target Engagement and Cellular Entry for PROTACs
Synopsis
- Target engagement and cellular entry are potential limiters to efficacy for E3 Ligase ligands and PROTACs
- We will present a NanoBRET™ Target Engagement based workflow to quantitatively assess cellular entry for un-derivatized E3 ligase ligands and PROTACs
- We will present applications of this workflow to the study of model ligands and PROTACs and demonstrate its utility within the broader degradation toolbox
10:40 am Live Panel Q&A – Ask the Speakers Your Burning Questions!
11:00 am
Morning Break & Speed Networking
Revealing Powerful Tools & Strategies for the Discovery of Novel E3’s & Effective Ligands
12:00 pm Unlocking the Ligandable Space with Ligase-centric PROTEINi Screening
Synopsis
- E3 ligases are a rich and under-exploited space for therapeutic ligand development
- We use our proprietary PROTEINi approach in an ultra-high throughput pooled phenotypic screening platform, exploiting high-diversity programmable drug mimetics
- Systematic application of these tools to ligand discovery has yielded a substantial cache of novel E3 ligase binders and peptide-based degraders which have been deployed to degrade key therapeutic targets
12:25 pm Discovery of Novel Ligands & Probes for E3 Ligases
Synopsis
- Chemical tools facilitate a better understanding of basic biology and therapeutic utility of E3 ligases
- Discussing new opportunities in understudied E3 complexes from novel E3 ligands
12:50 pm A Strategy to Assess the Cellular Activity of E3 Ligases Against Neo-Substrates Using Electrophilic Probes
Synopsis
- Chemical biology method to evaluate E3 ligases in cells for neosubstrate degradation
- Maleimide-thiol chemistry for Covalent Functionalization Followed by E3 Electroporation into live cells (COFFEE)
- Discovery of new E3 ligases amenable for targeted protein degradation
1:15 pm Live Panel Q&A – Ask the Speakers Your Burning Questions!
1:30 pm
Lunch Break & Networking
Reviewing & Characterizing E3’s to Harness the Full Potential of Effective & Selective Degradation
2:30 pm Computational Methods for Degrader Ternary Complex Prediction using HDX Data
Synopsis
- Recent crystal structures of degraders in ternary complexes highlight the flexibility of a ligase to accommodate different targets
- Computational modelling methods often struggle to identify the biologically relevant ternary complex
- Experimental derived data can be used to constrain models and support rational optimisation of degraders
2:55 pm Mapping the Degradable Kinome
Synopsis
- Provide unique chemical leads and chemo-proteomic data for over >200 protein kinases
- Quantified cellular and chemical variables on TPD
- Built a growing open access resource for chemo-proteomics data
3:20 pm Tissue-Specific Ubiquitin Ligases for Targeted Protein Degradation
Synopsis
- Targeted protein degradation (TPD) is an exciting new drug modality to unlock the undruggable genome
- Degradation of target proteins of interest in select tissues will enable broader applications for TPD
- Tissue-specific E3 ubiquitin ligases offer an opportunity for selective target degradation
3:45 pm Live Panel Q&A – Ask the Speakers Your Burning Questions!
4:00 pm
Afternoon Break & Networking
Characterizing Suitable Ligases for Rational Optimization of for PROTAC Degraders
4:30 pm Virtual Reality in SBDD: Exploring Complexes of the IMiDs and DDB1-CRBN E3 Ubiquitin Ligase in Nanome
Synopsis
- Understanding Nanome’s intuitive, state-of-the-art Virtual Reality ((VR) platform for viewing, manipulating, and modifying chemical and macromolecular structures in a fully immersive and collaborative 3D environment
- Examining the X-Ray structures (pdb ID’s: 4CI1, 4CI2, and 6H0F) of three related immunomodulatory drugs: thalidomide, lenalidomide, and pomalidomide in complex with DDB1-cereblon E3 ubiquitin ligase in VR
- Allowing a team of drug discovery scientists to view and interact with the protein degrader complexes in real time, fostering novel collaboration, ideas, and discoveries
4:55 pm New Insights into PROTAC-based Target Validation Strategies
Synopsis
- Discussing new insights in target validation (dTAG technologies) to assess the therapeutic potential of targeting unwanted proteins for the
treatment of disease - Exploring new dTAG strategies to target proteins using protein degrader technology
- Sharing new insights into target validation by modelling the systems in vivo
5:20 pm Benchmarking Selection & Design of New E3 Ligases for PROTACS
Synopsis
- Discussing key attributes of E3 Ligases for PROTACS and potential selection studies
- Exploring a cascade design for E3 selection and warhead identification
- Elaborating on selective case studies
5:45 pm Effectively Harnessing E3’s for Rapid PROTAC Development
Synopsis
- Discussing how Progenra’s UbiProTM platform has been employed to discover and characterize E3 ligands
- Characterizing E3 ligands which are suitable for PROTAC applications
- Elaborate on the unique approach to the discovery, optimization, and characterization of novel E3 ligands in vitro and in vivo.
- Exploring specific examples of applying these novel ligands for generating PROTACs for degrading undruggable targets