生物活性

• 描述The 17α-hydroxylase/C17-20 lyase (as known as CYP17A1) is a key enzyme in the androgen biosynthetic pathway. Abiraterone Acetate is the acetate form of Abiraterone. Abiraterone is a potent inhibitor of both 17α-hydroxylase and C17-20 lyase with IC₅₀ values of 18 and 17 nM, respectively. In guinea pig adrenal cells, abiraterone at the dose of 10^-5 M almost completely inhibited ACTH-stimulated production of androstenedione and cortisol. Moreover, abiraterone is also an inhibitor of androgen receptor (AR). It displaced ligand from wild-type AR with an EC₅₀ value of 13.4 μM. Abiraterone (0.1 - 25 μM) also showed dose-proportional inhibitory effect on T877A-AR, G142VAR, P533S-AR, T575A-AR and H874Y-AR. In LNCaP and VCaP prostate cancer cells. Abiraterone at the concentrations of 0.1 - 5 μM decreased cell viability in a dose-dependent manner when compared to DMSO control. After the treatment of LuCaP23CR and LuCaP35CR prostate cancer xenografts with abiraterone for 21 days, the serum PSA level was rapidly declined and the tumor growth was significantly inhibited as compared to vehicle-treated group. Abiraterone administration also resulted in statistically significant improvement in the progression-free survival.
• 细胞研究
• Cell Data

  Cell Lines	Concentration	Assay Type	Time	Activity Description	Data Sources
  hamster V79MZh cells	-	Function assay	-	Inhibition of human CYP11B1 expressed in hamster V79MZh cells, IC50=1.61 μM	20550118
  hamster V79MZh11B1 cells	-	Function assay	-	Inhibition of human CYP11B1 expressed in hamster V79MZh11B1 cells, IC50=1.608 μM	18672868
  human PC3 cells	-	Cytotoxic assay	48 h	Cytotoxicity against human PC3 cells assessed as growth inhibition after 48 hrs by MTT assay, IC50=9.32 μM	24148837

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• 动物研究
  剂量	Mice: 200 mg/kg[3]
  给药途径	p.o.

• 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
  NCT01957436	Metastatic Prostate Cancer	Phase 3	Recruiting	December 2030	-
  NCT02160353	High Risk Localised Prostate C... more >>arcinoma Collapse <<	Phase 2	Recruiting	October 2020	Ireland ... more >> Cork University Hospital Recruiting Cork, Ireland Contact: Contact Person    021-4920014       Principal Investigator: Paul Kelly, Dr          St Luke's Hospital Recruiting Dublin, Ireland, 6 Contact: Contact Person    01-4065000       Principal Investigator: Pierre Thirion, Dr          University Hospital Galway Recruiting Galway, Ireland Contact: Contact Person    091-893487       Principal Investigator: Cormac Small, Dr Collapse <<
  NCT02656615	Prostate Cancer	Phase 2	Terminated(Lack of Patient acc... more >>rual) Collapse <<	-	Switzerland ... more >> Cantonal Hospital Chur Chur, Graubuenden, Switzerland, 7000 University Hospital Basel Basel, Switzerland, 4000 Cantonal Hospital St.Gallen St.Gallen, Switzerland, 9007 Collapse <<

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• 参考文献

• [1] Li R, Evaul K, et al. Abiraterone inhibits 3β-hydroxysteroid dehydrogenase: a rationale for increasing drug exposure in castration-resistant prostate cancer. Clin Cancer Res. 2012 Jul 1;18(13):3571-9.

  [2] Pinto-Bazurco Mendieta MA, et al. Synthesis, biological evaluation, and molecular modeling of abiraterone analogues: novel CYP17 inhibitors for the treatment of prostate cancer. J Med Chem. 2008 Aug 28;51(16):5009-18.

  [3] Liu C, Armstrong C, et al. Niclosamide enhances abiraterone treatment via inhibition of androgen receptor variants in castration resistant prostate cancer. Oncotarget. 2016;7(22):32210-20.