TPD
Revolutionary Approaches to Eliminate Disease-Causing Proteins
The Targeted Protein Degradation Platform at PI Health Sciences is designed around a fundamental shift in how therapeutic intervention is achieved, moving from functional inhibition of proteins to their selective elimination. Instead of transiently blocking activity, this approach leverages the cell’s own quality control systems to remove disease-causing proteins entirely, enabling sustained biological effects.
Targeted protein degradation (TPD) functions through a catalytic mechanism, where a single degrader molecule can trigger repeated degradation events. This sub-stoichiometric mode of action supports prolonged pharmacodynamic responses and differentiates degraders from traditional occupancy-driven small molecules. By operating at the level of protein turnover rather than enzyme inhibition, this strategy expands the range of tractable targets.
The platform applies a multi-pathway degradation approach, utilizing the ubiquitin-proteasome system, autophagy-lysosome pathways, and endosome-lysosome mechanisms. This enables coverage across diverse protein classes and cellular localizations, including intracellular proteins, membrane-associated targets, and extracellular disease drivers. As a result, target classes such as transcription factors, scaffolding proteins, and membrane proteins become addressable within a single integrated framework.
Our services combine AI-powered molecular design, expert-led medicinal chemistry, and mechanistic validation to support degrader programs in a structured and scalable manner. This integrated approach enables rational modality selection, informed degrader design, and systematic evaluation of degradation efficiency, forming the foundation for robust TPD discovery and downstream advancement.
List of Targeted Protein Degradation Modalities
Our Capabilities in TPD
01
Multi-Pathway Protein Degradation Expertise
Application of ubiquitin–proteasome, autophagy–lysosome, and endosome–lysosome pathways to enable degradation across diverse biological contexts.
02
Broad Degrader Modality Coverage
Support across PROTACs, molecular glues, LYTACs, AUTACs, AUTOTACs, ATTECs, AbTACs, and emerging degrader technologies.
03
AI-Enabled Degrader Design & Optimization
Structure-based design incorporating ternary complex prediction, docking, enumeration, and machine learning–supported linker optimization.
04
Mechanistic Validation & Characterization
Biophysical assays including SPR and TR-FRET, structural studies such as cryo-EM, and unbiased proteomics to confirm degradation mechanisms.
05
Target Class Flexibility
Applicability to intracellular, membrane-associated, and extracellular protein targets across multiple therapeutic contexts.
06
Integrated In Vivo Translation
PK/PD and efficacy studies supporting degrader evaluation and progression within unified TPD Research programs.
Frequently asked questions
We’re here to help with any questions you have about plans, pricing, and supported features.
How does PI Health Sciences approach degrader development across different degradation pathways?
PI Health Sciences evaluates target biology, cellular localization, and disease context to select the most appropriate degradation pathway. Ubiquitin–proteasome, autophagy–lysosome, and endosome–lysosome mechanisms are assessed in parallel, ensuring that degrader design is driven by biological feasibility and translational relevance rather than modality preference.
How is target suitability assessed during early degrader programs?
Target suitability is assessed through ligandability analysis, E3 ligase compatibility, ternary complex stability prediction, and cellular degradation validation. These data guide early go or no-go decisions and inform chemistry optimization strategies during TPD discovery.
What validation is performed to confirm true protein degradation rather than functional inhibition?
We apply orthogonal biochemical, cellular, and proteomic assays to confirm target protein depletion, pathway engagement, and degradation kinetics. This ensures mechanistic clarity and supports robust differentiation from occupancy-driven inhibition mechanisms.
How does the platform support progression toward IND-enabling studies?
Programs are advanced with early PK/PD integration, degradation durability assessment, and in vivo efficacy modeling. This generates coherent datasets that support candidate nomination and seamless transition into formal preclinical and regulatory workflows.
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Partner with PI Health Sciences to advance targeted protein degradation programs across proteasomal and lysosomal pathways, integrating AI-enabled design, chemistry expertise, and translational validation.