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ARCC-4
- Development stage
- Preclinical
- Lead developer
- Yale University
- Modality
- PROTACs (E3 ligase recruitment) → Targeted Protein Degraders (TPDs) → Small Molecules, Bivalent/Multivalent Binders → Multivalent & Scaffold-Based Small Molecules → Small Molecules
- Administration
- Oral
01
Overview
ARCC-4 is a preclinical-stage, low-nanomolar proteolysis-targeting chimera (PROTAC) designed to degrade the androgen receptor (AR). It is a heterobifunctional molecule consisting of the AR antagonist enzalutamide linked to a ligand for the von Hippel-Lindau (VHL) E3 ubiquitin ligase. By recruiting VHL to the AR, ARCC-4 facilitates the polyubiquitination and subsequent proteasomal degradation of the receptor. ARCC-4 has demonstrated robust degradation of both wild-type AR and various clinically relevant AR mutants (such as F876L, T877A, and H874Y) that are associated with resistance to traditional antiandrogen therapies like enzalutamide. Developed by Yale University and Arvinas, ARCC-4 is widely utilized as a high-quality chemical probe and research tool to investigate AR biology and mechanisms of resistance in prostate and breast cancers.
- Other names
- ARCC 4ARCC4ARCC-4
02
Targets
AR (Adrenergic receptors)VHL (Von Hippel–Lindau tumor suppressor protein)
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