生物活性

• 靶点	Androgen Receptor IC50:16nM

• 描述The androgen receptor (AR) and the androgen-AR signaling pathway play a significant role in male sexual differentiation and the development and function of male reproductive and non-reproductive organs ^[7]. ARN-509 is a competitive AR inhibitor (IC₅₀=16 nM) which is fully antagonistic to AR overexpression, a common and important feature of castration-resistant prostate cancer (CRPC). In castration-resistant LNCaP/AR cells, ARN-509 (< 10 μM; 3d) antagonized androgen-mediated induction or repression of mRNA expression-levels for 13 endogenous genes including PSA and TMPRSS2, and ARN-509 (< 10 μM) also antagonized the proliferative effect of R1881 (30pM). Following 17 days of treatment with ARN-509 (10 mg/kg/day) in a model of castration-resistant prostate cancer, androgen-driven luciferase reporter-gene activity was consistently reduced compared to vehicle, indicating AR inhibition by ARN-509 in vivo. In castrate mice bearing LNCaP/AR (cs) xenograft tumors, 8/10 ARN-509-treated (10 mg/kg/day) tumors regressed by >50% (volume) on day 28 ^[8].
• 细胞研究
• Cell Data

  Cell Lines	Concentration	Assay Type	Time	Activity Description	Data Sources
  LNCAP cells	-	Proliferation assay	3 days	Antiproliferative activity against human LNCAP cells after 3 days, IC50=0.174 μM	26046313
  PSN1 cells	-	Cytotoxicity assay	96 h	Cytotoxicity against human PSN1 cells after 96 hrs by ATP-lite luminescence assay, IC50=0.06 μM	22247788
  PSN1 cells	30 nM	Function assay	24 h	Induction of cell cycle arrest in human PSN1 cells assessed as accumulation at G2/M phase cells at 30 nM after 24 hrs by flow cytometry	22247788

• 动物研究
  剂量	Mice: 10 mg/kg - 100 mg/kg[3] (p.o.), 2 mg/kg[4] (p.o. or i.v.); 1 mg/kg[5] (i.v.)
  给药途径	p.o., i.v.
  动物药代数据	Animal Mice[4] Rats[6] Dose 2 mg/kg 10 mg/kg Administration p.o. or i.v. p.o. F 126% (p.o.) Vd 2.51 L/kg (i.v.) T1/2 24.7 h 7.4 ± 0.4 h Tmax 4.00 h (p.o.) 3.5 ± 0.6 h CL 1.17 mL/min/kg (i.v.) Cmax 855 ng/ml (p.o.) 946 ± 43 ng/ml MRT 10.7 ± 0.5 h AUC0→∞ 35,941 ng·h/ml (p.o.) 28,463 ng·h/ml (i.v.) 14,752 ± 1997 h·ng/ml

• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT03770455	Metastatic Castration-resistan... more >>t Prostate Cancer Collapse <<	Phase 2	Not yet recruiting	April 2024	United States, Louisiana ... more >> Tulane University School of Medicine Not yet recruiting New Orleans, Louisiana, United States, 70112 Contact: Charlotte Manogue, MPH    504-988-3908    cmanogue@tulane.edu    Contact: Gaynelle Davis, MS    504-988-6770    gdavis7@tulane.edu    Principal Investigator: Jodi L Layton, MD Collapse <<
  NCT03581500	Prostate Adenocarcinoma ... more >> PSA Level Greater Than Ten Stage IIB Prostate Cancer AJCC v8 Stage III Prostate Cancer AJCC v8 Stage IIIA Prostate Cancer AJCC v8 Stage IIIB Prostate Cancer AJCC v8 Stage IIIC Prostate Cancer AJCC v8 Stage IV Prostate Cancer AJCC v8 Stage IVA Prostate Cancer AJCC v8 Stage IVB Prostate Cancer AJCC v8 Collapse <<	Phase 2	Not yet recruiting	August 31, 2019	United States, Texas ... more >> M D Anderson Cancer Center Not yet recruiting Houston, Texas, United States, 77030 Contact       vkundra@mdanderson.org Collapse <<
  NCT02835508	Healthy	Phase 1	Completed	-	Japan ... more >> Kumamoto-Shi, Japan Collapse <<

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