Workshop A: 9.00- 12.00
Deconvoluting Intricate Cellular Processes to Fast-Track Target Validation & De-risk the Initiation of Induced Proximity Pipelines for Novel Targets
Synopsis
Precise target credentialing is indispensable for advancing induced proximity modalities beyond PROTACs, ensuring their specificity, efficacy, and safety. While PROTACs center on the directed degradation of target proteins, next-generation induced proximity modalities seek to intricately influence cellular processes by orchestrating close-proximity interactions between proteins. Whilst this poses huge therapeutic opportunity, it is paired with added complexities in validating the biological significance of selected targets, many of which are poorly elucidated, and strategically refining the design of molecules to induce proximity.
This workshop will discuss:
- How to define the criteria for selecting specific targets in induced proximity modalities beyond PROTACs?
- How to streamline deep biological deconvolution?
- What are the advancing experimental techniques for target validation?
- How to determine if novel induced proximity modalities offer improved efficiency to other modalities, for a given indication?
Workshop B: 1.00 – 4.00
Identifying Novel Protein Partners for DUBTACs to Expand the Viable Targets for Stabilization & Restoring Protein Function in New Disease Paradigms
Synopsis
DUBTACs present a vastly developing paradigm of induced proximity modalities with therapeutic utility for disorders linked to perturbed ubiquitin signaling, such as oncology and neurodegenerative conditions. Despite offering a novel avenue to modulate ubiquitin homeostasis beyond degradation, clinically relevant targets have yet to gain proof of concept. Attaining selective DUB and E3 ligase pairs confronts redundancies within the ubiquitin system and knowledge gaps in the repertoire of structurally distinct DUBs utilized. Hijacking a broader range of highly cooperative DUB-E3 ligase pairs is pivotal to unlocking the complete therapeutic potential of DUBTACs and broadening their application in precision medicine.
This workshop will discuss:
- How to systematically profile novel ligands for DUB recruitment?
- How to expand the repertoire of targeted DUBs?
- What targets are most benefited by DUBTACs?
- How to predict and validate if stabilizing the target confers functional benefit?
- What are the key design principles for DUBTACs?