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Ab-PROTAC 3
- Development stage
- Preclinical
- Lead developer
- Imperial College London
- Modality
- PROTACs (E3 ligase recruitment) → Targeted Protein Degraders (TPDs) → Small Molecules, Cytotoxic ADCs → Antibody-Drug Conjugates (ADCs) → Antibody Conjugates → Antibody-Based Therapeutics, Bivalent/Multivalent Binders → Multivalent & Scaffold-Based Small Molecules → Small Molecules
- Administration
- Intravenous
01
Overview
**Ab-PROTAC 3** is a preclinical trastuzumab-based antibody-PROTAC conjugate designed to achieve HER2-dependent degradation of bromodomain-containing protein 4. The conjugate uses trastuzumab to bind HER2-positive cancer cells and deliver an intracellularly activatable BRD4-directed PROTAC. Following HER2-mediated internalization and lysosomal trafficking, hydrolysis of the antibody linker releases an active JQ1-derived, von Hippel-Lindau-recruiting PROTAC that induces ubiquitin-proteasome-mediated BRD4 degradation. In published cell-line studies, Ab-PROTAC 3 selectively degraded BRD4 in HER2-positive breast-cancer cells while sparing HER2-negative cells. It was developed as a proof-of-concept approach for tissue-selective targeted protein degradation.
- Other names
- Ab-PROTAC 3Ab-PROTAC3Ab-PROTAC-3trastuzumab-PROTAC conjugate 3
02
Targets
BRD4 (Bromodomain-containing protein 4)VHL (Von Hippel–Lindau tumor suppressor protein)ERBB2 (Erb-b2 receptor tyrosine kinase 2)
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