AZD3514

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

AZD3514 是一种有效的口服雄激素受体下调剂，Ki 为 2.2 μM，具有降低 AR 蛋白表达的能力。第 1 阶段。

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 (0-10 μM/L; 7 d) inhibits LNCaP and LAPC4 cells proliferation.AZD3514 (0-10 μM/L; 24 h) inhibits the ligand-driven expression of known AR-regulated genes.AZD3514 (0-30 μM/L; 24 h) reduces AR protein expression in LNCaPs and LAPC4s.AZD3514 (1-10 μM/L; 2 h) reduces AR nuclear translocation in LNCaP cells. :Cell Proliferation Assay Cell Line:LNCaP and LAPC4 cell lines Concentration:0, 0.1, 0.4, 1.1, 3.3 and 10 μM/LIncubation Time:7 daysResult:Inhibited LAPC4 cells growth and dose-dependently inhibited proliferation of LNCaP cells.Western Blot AnalysisCell Line:LNCaP and LAPC4 cell lines Concentration:0, 0.4, 1.1, 3.3, 10 and 30 μM/L Incubation Time:0-24 hours Result:Dose-dependently reduced AR protein expression in LNCaPs, and decreased AR protein in LAPC4 cells with a concentration of 10 μM/L. Reduced the rate of AR synthesis to reduce the concentration of AR protein.RT-PCRCell Line:LNCaP and LAPC4 cell lines Concentration:0, 0.4, 1.1, 3.3 and 10 μM/L Incubation Time:24 hours Result:Inhibited ligand-driven expression of AR-regulated genes PSA and TMPRSS2 in both LNCaP and LAPC4 cells.

AZD3514 (10-100 mg/kg; p.o. once daily for 6 days) inhibits AR signaling in rats.AZD3514 (50 mg/kg; p.o. once daily for 30 days) inhibits prostate tumor growth.AZD3514 (50-100 mg/kg; p.o. once daily for 3 days) significantly reduces nuclear AR protein in vivo. Animal Model:Intact or castrat 42- and 49-day-old Hans Wistar rats Dosage:10, 50 and 100 mg/kg Administration:Oral gavage; 10-100 mg/kg once daily; for 6 days Result:Inhibited AR signaling in rats, reduced seminal vesicle weight in intact rats, and inhibited the ability of exogenous testosterone proprionate to cause an increase in seminal vesicle weight in castrated rat. Animal Model:Male Copenhagen rats with Dunning R3327H prostate tumors Dosage:50 mg/kg Administration:Oral gavage; 50 mg/kg once daily; for 30 days Result:Significantly inhibited prostate tumor growth of rats.

AZD3514 | AZD 3514 | AZD-3514

Endocrinology/Hormones

Androgen Receptor (AR)

Androgen Receptor

Cancer

——

1240299-33-5

519.56

C??H??F?N?O?

>98% (HPLC)

DMSO:93 mg/mL (179 mM);Ethanol:93 mg/mL (179 mM);Water:<1 mg/mL

CC(N1CCN(CCOC2=CC=C(C3CCN(C4=NN5C(CC4)=NN=C5C(F)(F)F)CC3)C=C2)CC1)=O

1-(4-(2-(4-(1-(3-(trifluoromethyl)-7,8-dihydro-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)piperidin-4-yl)phenoxy)ethyl)piperazin-1-yl)ethanone

(-20℃)

With Ice Pack

≥ 2 years