Protein Degrader Discovery and Screening Services
The development of protein degrader (Proteolysis Targeting Chimeras) is transforming the field of drug discovery, enabling the selective degradation of disease-related proteins. The iterative optimization of protein degraders often relies heavily on empirical methods, requiring extensive compound synthesis and high-throughput screening strategies. Traditional protein immunoblotting methods, like Western blot, remain the gold standard for evaluating protein degrader activity but are time-intensive and impractical for large-scale compound library screening. Therefore, achieving robust and high-throughput screening strategies is essential for the successful development of protein degraders.
Comprehensive Protein Degrader Services
Creative Biogene offers an end-to-end solution for protein degrader development, integrating advanced computational screening, experimental validation, and optimization strategies to accelerate your drug discovery process.
1. Strategic E3 Ligase Selection
Effective E3 ligase selection is critical to the success of protein degraders. Creative Biogene employs a data-driven approach to select ligases that align with your project goals:
- CRBN and VHL as Primary Systems:
These ligases are prioritized for their versatility and proven success in protein degrader development.
For specialized requirements, we offer options like cIAP1, MDM2, KEAP1, DCAF15, and RNF114.
- Customized Ligase Solutions
Our team tailors ligase selection based on the target protein's compatibility and the cellular environment.
2. Virtual Screening
Efficient and Accurate Protein Degrader Discovery
Our protein degrader virtual screening services leverage computational tools to reduce the need for excessive compound synthesis and biological evaluation, significantly enhancing throughput.
- AI-Driven Molecular Design: We employ an advanced deep neural network model—based on the structural information of target proteins (POIs) and E3 ligases, enabling accurate predictions of the degradation efficiency of specific protein degraders. By deeply embedding various parts of the POI-Protein Degrader-E3 ligase complex, the model processes the data through multiple neural network modules, ultimately using a multi-layer perceptron (MLP) to make precise predictions.
- High-Throughput Molecular Docking: Based our extensive protein degrader library resources, we employ advanced multi-task docking techniques to model the interactions between the target protein, E3 ligase, and protein degrader molecules.
- Database-Driven Predictions: Using the protein degrader database and integrating biological activity data, we evaluate the degradation potential and activity of protein degrader candidates based on the pocket environments of target proteins and E3 ligases.
- Comprehensive Structure and Dynamics Analysis: Our screening approach supports high-throughput evaluation while offering detailed insights into structural predictions and dynamic analyses for design refinement.
3. Experimental Screening and Validation
Once virtual screening identifies promising candidates, our robust experimental pipeline ensures accurate validation and optimization:
- High-Throughput Phenotypic Screening Service:
Cell Proliferation Inhibition Assays: Assess compound activity using CCK-8 kits to measure cell growth inhibition.
Luciferase-Based Protein Degrader Screening: Evaluate protein degrader performance on a large scale through luciferase reporter assays, quantifying target protein degradation. - Mass Spectrometry Detection: Perform TMT-labeling proteomics to compare the proteome of active protein degrader-treated cells with that of active drug molecule-treated and non-active protein degrader-treated cells. This approach ensures the identification of potential targets and comprehensive profiling of cellular responses.
- Protein Degradation Assays: Confirm target protein degradation via SDS-PAGE electrophoresis and Western blot techniques.
- Target Interaction Analysis: Use biotin, fluorescent, or photo-crosslinking probes to confirm direct interactions between protein degraders and target proteins. Conduct affinity assays such as Surface Plasmon Resonance (SPR), MicroScale Thermophoresis (MST), or Isothermal Titration Calorimetry (ITC) to measure the binding strength and validate target engagement.
Figure 1. Comprehensive Screening Workflow for Protein Degraders.
Why Choose Creative Biogene?
- Proven Expertise: Our experienced team combines deep expertise in chemistry, molecular biology, and computational drug design to deliver superior protein degrader solutions.
- Advanced Platforms: We utilize innovative technologies like AI-driven modeling, database integration, and high-throughput experimental screening to streamline protein degrader development.
- Customized Solutions: Our services are tailored to your unique requirements, from virtual screening and E3 ligase selection to large-scale validation and optimization.
- Global Reach: With a robust quality and compliance system, our services meet international regulatory standards, supporting customers worldwide in drug discovery and development.
Start Your Protein Degrader Journey with Us
Creative Biogene is committed to accelerating your protein degrader development by providing reliable, high-throughput, and innovative solutions. Contact us today to explore how our expertise can bring your project closer to success!
* For research use only. Not intended for any clinical use.
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