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BCL6 PROTAC
- Development stage
- Preclinical
- Lead developer
- Arvinas
- Modality
- PROTACs (E3 ligase recruitment) → Targeted Protein Degraders (TPDs) → Small Molecules, Bivalent/Multivalent Binders → Multivalent & Scaffold-Based Small Molecules → Small Molecules
01
Overview
BCL6 PROTAC is a small molecule proteolysis-targeting chimera (PROTAC) designed to induce the degradation of the B-cell lymphoma 6 (BCL6) protein. Developed by AstraZeneca, this therapeutic modality targets BCL6, a transcription factor that acts as a master regulator of the germinal center reaction and is frequently deregulated in B-cell lymphomas, such as diffuse large B-cell lymphoma (DLBCL). The PROTAC molecule functions by recruiting the Von Hippel-Lindau (VHL) E3 ubiquitin ligase to BCL6, facilitating its ubiquitination and subsequent degradation by the 26S proteasome. Preclinical in vitro studies demonstrated that the compound could achieve approximately 80% degradation of BCL6 across all cellular compartments and exhibited favorable drug metabolism and pharmacokinetics (DMPK) properties. However, the program did not advance to in vivo testing or clinical development.
- Other names
- BCL6 degraderBCL-6 degraderBCL 6 degrader
02
Targets
CRBN (Cereblon)BCL6 (B cell lymphoma 6 protein)
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