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BRD4 degrader 4
- Development stage
- Preclinical
- Lead developer
- Genentech
- Modality
- PROTACs (E3 ligase recruitment) → Targeted Protein Degraders (TPDs) → Small Molecules, Bivalent/Multivalent Binders → Multivalent & Scaffold-Based Small Molecules → Small Molecules
- Administration
- Intravenous
01
Overview
BRD4 degrader 4 is a potent, small-molecule proteolysis-targeting chimera (PROTAC) designed to induce the selective degradation of Bromodomain-containing protein 4 (BRD4). Developed by Genentech, it consists of a BRD4-binding moiety (typically a thienotriazolodiazepine analog) linked to a ligand for the von Hippel-Lindau (VHL) E3 ubiquitin ligase. By recruiting the VHL E3 ligase complex to BRD4, the compound facilitates the ubiquitination and subsequent proteasomal degradation of the target protein. BRD4 degrader 4 has been extensively evaluated as a payload for antibody-degrader conjugates (ADCs or DACs), where it is conjugated to monoclonal antibodies (such as anti-HER2 or anti-CLL1) to enable targeted protein degradation in specific cell types, thereby reducing systemic toxicity and improving the therapeutic index of BET domain inhibitors in oncology.
- Other names
- VHL-recruiting BRD4 PROTAC
02
Targets
BRD4 (Bromodomain-containing protein 4)VHL (Von Hippel–Lindau tumor suppressor protein)
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