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dBET6
- 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
- Intranasal
01
Overview
dBET6 is a proteolysis-targeting chimera (PROTAC) designed to induce the rapid and selective degradation of bromodomain-containing protein 4 (BRD4) and other BET family proteins. It is a bifunctional small molecule consisting of the BET inhibitor JQ1 conjugated to thalidomide, which recruits the Cereblon (CRBN) E3 ubiquitin ligase. By bringing CRBN into proximity with BRD4, dBET6 facilitates the polyubiquitination and subsequent proteasomal degradation of the target protein. This mechanism leads to more potent and sustained inhibition of oncogenic signaling compared to traditional BET inhibitors. dBET6 is widely utilized as a chemical probe in research and is being investigated for therapeutic applications in various cancers, including pediatric high-grade gliomas and diffuse midline gliomas (DMG). Due to its large molecular size and poor blood-brain barrier penetration, researchers are exploring specialized delivery methods such as intranasal administration using immunopolymersomes to target brain tumors effectively.
- Other names
- dBET6dBET-6dBET 6
02
Targets
BRD3 (Bromodomain-containing protein 3)BRD4 (Bromodomain-containing protein 4)BRD2 (Bromodomain-containing protein 2)CRBN (Cereblon)BRDT (Bromodomain testis-specific protein)
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