AR Degrader-3 

AR Degrader-3 is an orally active molecular glue that targets AR/ARV7 and induces the degradation of AR and ARV7 through the ubiquitin-proteasome pathway (UPP). AR Degrader-3 directly interacts with the ligand-binding domain (LBD) and the N-terminal domain (NTD) of AR. AR Degrader-3 effectively suppresses the transcriptional activity of wild-type AR (AR-WT), AR mutants, and ARV7. AR Degrader-3 downregulates the mRNA and protein levels of downstream AR target genes, thereby overcoming antiandrogen resistance mediated by ARV7 and AR point mutations. AR Degrader-3 induces apoptosis in Enzalutamide (HY-70002) (ENZa)-resistant cells and increases cleaved caspase-3 protein levels. AR Degrader-3 can be used for the study of castration-resistant prostate cancer (CRPC)^[1].

AR Degrader-3 (Compound A6) (0.2-5 μM, 24 h) broadly inhibits AR transcriptional activity by dose-dependently suppressing both exogenous and endogenous AR in PC-3 and C4-2 cells; additionally, it significantly suppresses endogenous AR and ARV7 in ENZa-resistant 22Rv1 cells, and inhibits the transcriptional activities of AR mutants (W741L, T877A, F876L) in PC-3 cells^[1].
AR Degrader-3 (0.078-10 μM, 0-36 h) dose-dependently suppresses ARV7 (DC₅₀ = 0.24 μM) protein level in 22Rv1 cells, powerfully down-regulates AR (DC₅₀ = 0.18 μM) protein level in C4-2 cells, and down-regulates ARV7 protein levels in a time-dependent manner^[1].
AR Degrader-3 potently inhibits AR and ARV7 by directly binding to both AR-LBD (IC₅₀ = 105.4 nM) and AR-AF1 (K_D = 23.0 μM ) in LNCaP cells^[1].
AR Degrader-3 (1-5 μM, 4-8 h) degrades AR and ARV7 through the ubiquitin-proteasome pathway (UPP), as evidenced by its dose-dependent reduction of AR and ARV7 protein but not mRNA levels in C4-2 and 22Rv1 cells, respectively; by demonstrating accelerated degradation upon cycloheximide treatment; by showing that the protein level reduction was counteracted by MG132; and by markedly inducing AR ubiquitination^[1].
AR Degrader-3 (72 h) inhibits the proliferation of C4-2 cells (IC₅₀ = 0.59 μM) and 22Rv1 cells (IC₅₀ = 1.4 μM), but has little effect on DU145 (IC₅₀ > 50 μM) and PC-3 (IC₅₀ = 48.6 μM) cells^[1].
AR Degrader-3 (0.2-5 μM, 8-24 h) blocks R1881-induced PSA protein expression in a dose-dependent manner and reduces the mRNA levels of PSA and PMEPA1 in 22Rv1 cells^[1].
AR Degrader-3 (1-2 μM, 14 days) selectively decreases 22Rv1 cells colony numbers but shows no influence on AR-negative PC-3 cells colony numbers and promotes the apoptosis of the 22Rv1 cells^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

AR Degrader-3 (Compound A6) (15-30 mg/kg, p.o., once daily for 14 days) effectively inhibits the growth of CRPC tumors in 22Rv1 cell xenograft mice in vivo, and no significant toxicity is observed^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

435.50

C₂₃H₂₁N₃O₄S

1182011-65-9

CC1=NOC(C)=C1COC2=CC=C(C(NC3=NC(C4=CC=C(OC)C=C4)=CS3)=O)C=C2

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Zhang R, et al. Development of dual AR/ARV7 degraders with 3,5-dimethylisoxazole to overcome antiandrogen resistance in castration-resistant prostate cancer. Eur J Med Chem. 2026 Jan 5;301:118259.