Molecular Formula | C25H32F3N7O2 |
Molar Mass | 519.56 |
Density | 1.41±0.1 g/cm3(Predicted) |
Boling Point | 669.5±65.0 °C(Predicted) |
pKa | 6.31±0.10(Predicted) |
Storage Condition | -20℃ |
In vitro study | AZD3514 binds to the AR ligand binding domain and binds to AR more selectively than to other nuclear hormone receptors. In vitro, AZD3514 acts on prostate cancer cells expressing wild-type (VCaP) and mutant (T877A),AR(LNCaP), to inhibit cell growth, but has no effect on AR-negative prostate cancer cells. In vitro, AZD3514 acts on LNCaP cells to rapidly reduce PSA synthesis and significantly reduce PSA mRNA within 2-3 hours. AZD3514 acts on LNCaP cells and U2OS transfected AR cells to inhibit androgen-induced translocation of AR from cytoplasm to nucleus. AZD3514 treatment of LNCaP cells under hormone-depleted conditions also reduced AR protein, with a significant effect seen within 6-8 hours, with a maximal effect at 18-24 hours. Under such conditions, the ability to down-regulate AR can be used to distinguish AZD3514 from the AR antagonists Bicalutamide and Enzalutamide, which do not reduce AR protein levels. |
In vivo study | AZD3514 orally treated at a dose of 100mg/kg once a day for 7 consecutive days significantly inhibited the growth of sexual appendages induced by Testosterone. The mode of action of AZD3514 is associated with loss of AR function. AZD3514 was orally treated daily at a dose of 100 mg/kg in copenchagen rats bearing R3327H Dunning prostate tumors for 3 days, indicating that AZD3514 treatment can also reduce tumor AR in vivo. |
1mg | 5mg | 10mg | |
---|---|---|---|
1 mM | 1.925 ml | 9.624 ml | 19.247 ml |
5 mM | 0.385 ml | 1.925 ml | 3.849 ml |
10 mM | 0.192 ml | 0.962 ml | 1.925 ml |
5 mM | 0.038 ml | 0.192 ml | 0.385 ml |
biological activity | AZD3514 is an oral effective androgen receptor (androgen receptor) inhibitor with Ki of 2.2 μM and reduced AR protein expression. Phase 1. |
target | TargetValue Androgen Receptor 2.2 μM(Ki) |
Target | Value |
Androgen Receptor | 2.2 μM(Ki) |
In vitro studies | AZD3514 bind to the AR ligand binding domain, and binding to AR is more selective than binding to other nuclear hormone receptors. In vitro, AZD3514 acts on prostate cancer cells expressing wild-type (VCaP) and mutant (T877A),AR(LNCaP), inhibiting cell growth, but has no activity on AR-negative prostate cancer cells. In vitro, AZD3514 acts on LNCaP cells, and within 2-3 hours, rapidly reduces PSA synthesis and significantly reduces PSA mRNA. AZD3514 acts on LNCaP cells and U2OS transfected AR cells to inhibit androgen-induced AR translocation from cytoplasm to nucleus. AZD3514 treatment of LNCaP cells under hormone depletion conditions also reduced AR protein, and obvious effects were seen within 6-8 hours, and the maximum effect was achieved within 18-24 hours. Under such conditions, the ability to downregulate AR can be used to distinguish between AZD3514 and AR antagonist Bicalutamide and Enzalutamide, the latter two do not reduce AR protein levels. |
in vivo study | AZD3514 was treated orally at a dose of 100 mg/kg once a day for 7 consecutive days, significantly inhibiting Testosterone-induced growth of sexual accessory organs. The mode of action of AZD3514 is related to the loss of AR function. AZD3514 Copenhagen rats carrying R3327H Dunning prostate tumors were treated orally at a daily dose of 100 mg/kg for 3 days, indicating that AZD3514 treatment could also reduce tumor AR in vivo. |