Sigma-Aldrich Ar/Ar-V7 Degrader 27C

Potent and selective inducer of E3 ligase MDM2-mediated degradation of androgen receptor (AR) and the constitutively active splice variant AR-V7.
Compound 27c (cpd 27c) is a potent and selective inducer of E3 ligase MDM2-mediated degradation of androgen receptor (AR) and the constitutively active splice variant AR-V7 (DC50 = 2.67 and 2.64 μM, respectively, post 24h treatment in 22RV1 cells). Cpd 27c selectively inhibits AR-dependent proliferation in prostate cancer cultures (IC50 = 0.9 μM/22RV1 and 1.4 μM/LNCaP, >50 μM/AR-neg DU-145) and exhibits antitumor efficacy in an enzalutamide-resistant 22RV1 xenograft model in mice in vivo (10 or 30 mg/kg vial daily i.v.) by suppressing AR signaling pathway transcriptional activity.