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The majority of proteins and their abundance is regulated via the ubiquitin proteasome system (UPS), which uses ubiquitin conjugation to signal proteins that should be trafficked to the proteasome for degradation. Targeting proteins for degradation via the UPS with small-molecule degraders such as PROTACs or molecular glues is also emerging as a new modality for small-molecule drug development. NanoBRET technology is a proximity-based method dependent upon energy transfer from a luminescent donor target protein to a fluorescent acceptor. The target protein fused to NanoLuc luciferase or complemented NanoBiT luciferase serves as the bioluminescent BRET energy donor. HaloTag fusions are labeled with the HaloTag NanoBRET 618 fluorescent ligand and serve as the energy acceptor. Interactions will result in energy transfer between the donor and acceptor, resulting in increased NanoBRET signal.
