Validated TR-FRET Assays and Reagents to Accelerate PROTAC, Molecular Glue, and Ubiquitination Research
Targeted protein degradation has emerged as a powerful therapeutic strategy, placing E3 ligases at the center of drug discovery efforts in oncology and precision medicine. However, studying E3 ligase activity remains technically challenging due to the complexity of ubiquitination pathways and the risk of assay artifacts.
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In partnership with LifeSensors, a recognized expert in ubiquitin biology, Tebubio provides access to robust, validated assays and reagents for E3 ligase screening and profiling. | |||
Together, we support researchers with reliable tools to investigate ubiquitination mechanisms, identify true ligase modulators, and accelerate PROTAC and molecular glue discovery.
E3 Ligase TR-FRET Assay
LifeSensors has developed reagents and assays encompassing both traditional and non-traditional approaches for E3 ligase screening and profiling. Quickly distinguishing true hits from false positives, developing structure-activity relationships, and establishing rank order potency from purified enzymes to cellular models, are key steps to success.
Example of E3 TR-FRET assay and inhibitor dose response curve.
Protein X was used as a substrate of this E3 ligase. After initial TR-FRET high throughput screening, selected candidates were used to analyze IC50 by titration assay.
LifeSensors’ E3 TR-FRET detection system utilizes their TUBE technology to monitor E3 ligase activity by fluorescence signal. This assay involves donor-labeled TUBEs that bind to acceptor-labeled polyubiquitin chains synthesized by the target E3 ligase.
When donor-labeled TUBEs come in close proximity to polyubiquitin chains containing acceptor-labeled ubiquitin will yield in a FRET signal. This signal can be monitored over time in a homogenous, high-throughput format, making it ideal for small molecule screening to find tool compounds for E3 ligases.
Technology Highlights
- Ubiquitination cascade kits: UC105, UC104
- PROTAC and Molecular Glue Screening kits: PA950, PA770, MG780
- Access to 50+ E3 ligases for performing discovery and selectivity studies in rapid homogenous assay format
- E1-E2-E3 Inhibitors
Together with LifeSensors, Tebubio offers a comprehensive set of products supporting E3 ligase and ubiquitin research workflows, from basic enzymology to drug discovery and cellular validation.
Further readings:
- Understanding E3 Ligase Classifications - Multi-scale classification decodes the complexity of the human E3 ligome – Dutta et.al, Nature Communications, (2025) 16:11382.
- PROTAC, Molecular Glue & DUBTAC Discovery Tools | Targeted Protein Degradation
- Ubiquitination & Targeted Protein Degradation Tools
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References
Article content created by Tebubio using courtesy materials provided by LifeSensors.
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