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dTAG degrader
- Development stage
- Preclinical
- Lead developer
- Dana-Farber Cancer Institute
- Modality
- PROTACs (E3 ligase recruitment) → Targeted Protein Degraders (TPDs) → Small Molecules, Bivalent/Multivalent Binders → Multivalent & Scaffold-Based Small Molecules → Small Molecules
- Administration
- Intraperitoneal
01
Overview
The dTAG (degradation tag) system is a targeted protein degradation (TPD) platform used for the rapid and reversible depletion of proteins in biological systems. It utilizes heterobifunctional small molecules, known as dTAG degraders, which consist of a ligand selective for the mutant protein FKBP12(F36V) linked to an E3 ligase recruiter (such as thalidomide for CRBN or a VHL ligand). When a protein of interest (POI) is genetically fused to the FKBP12(F36V) tag, the dTAG degrader facilitates the formation of a ternary complex between the tagged POI and the E3 ligase, leading to polyubiquitination and subsequent proteasomal degradation. This system is widely used as a research tool for target validation and studying protein function in various disease models, including multiple myeloma, breast cancer, and Ewing sarcoma.
- Other names
- dTAGdegradation tag degraderFKBP12(F36V) degrader
02
Targets
FKBP1ACRBN (Cereblon)VHL (Von Hippel–Lindau tumor suppressor protein)
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