Molecular Weight(MW): 519.56
AZD3514 is a potent and oral androgen receptor downregulator with Ki of 2.2 μM and has ability of reducing AR protein expression.Phase 1.
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|Description||AZD3514 is a potent and oral androgen receptor downregulator with Ki of 2.2 μM and has ability of reducing AR protein expression.Phase 1.|
AZD3514 binds to the AR ligand binding domain and has selectivity for binding to AR over other nuclear hormone receptors. In vitro AZD3514 inhibits cell growth in prostate cancer cells expressing wild-type (VCaP) and mutated (T877A) AR (LNCaP), but is inactive in AR-negative prostate cancer cells. AZD3514 causes a rapid reduction in PSA synthesis in vitro; with a significant decrease in PSA mRNA being evident in LNCaP cells within 2-3 h of compound treatment. AZD3514 inhibits an androgen-induced translocation of AR from the cytoplasm to the nucleus within a comparable time-frame in LNCaP cells and U2OS AR-transfected cells. AZD3514 treatment also reduces AR protein in LNCaP cells maintained in steroid-depleted conditions; an effect which is evident within 6-8 h, and maximal at 18-24 h. The ability to down-regulate AR under such conditions differentiates AZD3514 from the AR antagonists bicalutamide and Enzalutamide, which do not reduce AR protein levels. 
|In vivo||Oral administration of AZD3514 (100mg/kg once-daily for 7 days) significantly inhibits testosterone-induced growth of sexual accessory organs. The mode of action of AZD3514 is associated with loss of AR function. Administration of AZD3514 (100 mg/kg/day orally) for 3 days to Copenhagen rats bearing R3327H Dunning prostate tumours, indicates that AZD3514 treatment also reduces tumour AR in vivo. |
|In vitro||DMSO||100 mg/mL (192.47 mM)|
|Ethanol||100 mg/mL (192.47 mM)|
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