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AZD5335 (AstraZeneca)
- Development stage
- Unknown
- Lead developer
- AstraZeneca
- 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
AZD5335 is an orally bioavailable proteolysis-targeting chimera (PROTAC) developed by AstraZeneca for the treatment of metastatic castration-resistant prostate cancer (mCRPC). It functions by recruiting the Von Hippel-Lindau (VHL) E3 ubiquitin ligase to the androgen receptor (AR), leading to the ubiquitination and subsequent degradation of the AR protein via the proteasome. This mechanism allows for the depletion of both wild-type AR and various mutant forms, such as AR-V7 and L702H, which are often associated with resistance to standard-of-care anti-androgen therapies like enzalutamide or abiraterone. AZD5335 is currently being evaluated in clinical trials both as a monotherapy and in combination with other agents to overcome resistance in advanced prostate cancer.
- Other names
- androgen receptor PROTACAR PROTAC
02
Targets
VHL (Von Hippel–Lindau tumor suppressor protein)AR (Adrenergic receptors)
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