PROTACs (PROtein TArgeting Chimeras) artificially hijack the components of the UPS (Ubiquitin Proteasome System) to degrade a target protein, founding the concept of PROTAC drug discovery. PROTAC drugs are hetero-bifunctional small molecules that contain two functional ligands connected via a linker; one ligand binds to a target protein and the other ligand binds to an E3 ligase.

In contrast, DUBTACs (Deubiquitinase Targeting Chimeras) exploit the same ubiquitin–proteasome system but are designed to stabilize, rather than degrade, a target protein. Instead of recruiting an E3 ligase, DUBTACs are hetero-bifunctional molecules that bring a deubiquitinase (DUB) into proximity with a specific target protein. By binding both the target protein and a DUB, DUBTACs promote removal of ubiquitin chains that would otherwise signal proteasomal degradation. This targeted deubiquitination preserves protein abundance and function, enabling therapeutic intervention in diseases driven by aberrant protein loss. Together, PROTACs and DUBTACs represent complementary approaches for modulating protein fate through precise manipulation of the UPS.

With tremendous excitement surrounding the field of targeted protein degradation, there is an unmet need for functional assays that can study the effects of PROTACs on the ubiquitination of a target(s) and subsequent degradation. Traditional methods such as western blotting and reporter gene assays have been at the forefront to study PROTAC and molecular glue mediated degradation. However, these methods are extremely low-throughput, time-consuming, and/or prone to artifacts.

To address this gap, LifeSensors has developed a comprehensive suite of ubiquitin-focused assay platforms designed to directly interrogate the key mechanistic steps underlying molecular glue–mediated protein degradation. These assays enable quantitative measurement of ubiquitination, E3 ligase activity, and substrate engagement in formats that are scalable and compatible with high-throughput screening. By leveraging defined biochemical systems and ubiquitin pathway reagents, LifeSensors’ approaches allow researchers to move beyond indirect readouts of protein loss and instead monitor glue-induced ubiquitin transfer and chain formation with high sensitivity and reproducibility. Importantly, this collection of assays is well suited to the unique challenges of molecular glues, capturing transient and weak interactions that are difficult to detect using traditional methods. Together, these tools provide a mechanistically rich framework for screening, validating, and optimizing molecular glues, accelerating discovery while reducing reliance on low-throughput, artifact-prone techniques.