Synonyms: ARD2585 | compound 43 [PMID: 34473519]
Compound class:
Synthetic organic
Comment: ARD-2585 is a highly potent and orally bioavailable PROTAC androgen receptor (AR) degrader molecule [1]. It was designed to reduce AR in metastatic castration-resistant prostate cancer (mCRPC), as an alternative mechanism to antagonising AR signaling with drugs such as enzalutamide and apalutamide. Structurally ARD-2585 is a bifunctional molecule that contains an AR antagonist ligand linked to a cereblon binding component, that targets the AR to the cereblon/cullin 4A E3 ligase complex for degradation. It shares structural similarities to bavdegalutamide, which was the first AR PROTAC to advance to clinical evaluation in humans.
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Bioactivity Comments |
In vitro ARD-2585 degrades AR in LNCaP and VCaP cells with a DC50 value of 0.01-0.04 nM, and inhibits VCaP cell growth with an IC50 of 1.5 nM [1]. In contrast ARV-110's DC50 is 1.6 nM and it inhibits VCaP cell growth with an IC50 value of 30.4 nM. |