Abiraterone Acetate

Names

[ Name ]:
Abiraterone Acetate

[Synonym ]:
17-(3-pyridyl)-5,16-androstadien-3beta-acetate
Abiraterone acetate
Androsta-5,16-dien-3-ol, 17-(3-pyridinyl)-, acetate (ester), (3β)-
Zytiga
(3β)-17-(3-Pyridinyl)androsta-5,16-dien-3-yl acetate
(3β)-17-(pyridin-3-yl)androsta-5,16-dien-3-yl acetate
Abiraterone (acetate)

Biological Activity

[Description]:

Abiraterone acetate is an oral, potent, selective, and irreversible inhibitor of CYP17.

[Related Catalog]:

Signaling Pathways >> Metabolic Enzyme/Protease >> Cytochrome P450

Research Areas >> Cancer

[Target]

CYP17[1]

[In Vitro]

Abiraterone (Abi) acetate is an ester prodrug of the anticancer agent Abiraterone, which shows IC50 values of 15 nM and 2.5 nM for the 17,20-lyase and 17α-hydroxylase (CYP17 is a bifunctional enzyme with both 17α-hydroxylase and 17,20-lyase activity). Abiraterone inhibits human 17,20-lyase and 17α-hydroxylase with IC50 of 27 and 30 nM respectively[1]. Significant inhibition of proliferation of the AR-positive prostate cancer cell lines LNCaP and VCaP with doses of Abiraterone ≥5 μM is confirmed[2]. Abiraterone inhibits recombinant human 3βHSD1 and 3βHSD2 activity with competitive Ki values of 2.1 and 8.8 μM. 10 μM Abiraterone is sufficient to completely block synthesis of 5α-dione and DHT in both cell lines.Treatment with Abiraterone significantly inhibited CRPC progression in the robustly growing subset, effectively putting a ceiling on tumor growth over 4 weeks of treatment (P<0.00001)[3].

[In Vivo]

Abiraterone (Abi) acetate prolongs survival in castration-resistant prostate cancer (CRPC). [3H]-dehydroepiandrosterone (DHEA) depletion and Δ4-androstenedione (AD) accumulation are inhibited by Abiraterone in LNCaP, with an IC50<1 μM. The 0.5 mmol/kg/d Abiraterone treatment dose is previously shown to yield serum concentrations of about 0.5 to 1 μM. Xenograft tumor growth in the control group is widely variable, with some tumors growing slowly and only a subset of tumors exhibiting robust growth[3].

[Cell Assay]

LNCaP and VCaP cells are seeded in 96-well plates and grown in CSS-supplemented phenol red-free or FBS-supplemented media for 7 days. Cells are treated with Abiraterone (5 μM and 10 μM) at 24 and 96 hours after plating and cell viability is determined on day 7 by adding CellTiter Glo and measuring luminescence[2].

[Animal admin]

Mice[3] Male NOD/SCID mice 6 to 8 weeks of age are surgically orchiectomized and implanted with a 5 mg 90-day sustained release DHEA pellet to mimic CRPC with human adrenal physiology. Two days later, 7×106 LAPC4 cells are injected subcutaneously with Matrigel. Tumor dimensions are measured 2 to 3 times per week, and volume is calculated as length×width×height×0.52. Once tumors reach 300 mm3, mice are randomly assigned to vehicle or Abiraterone treatment groups. Mice in the Abiraterone group are treated with 5 mL/kg intraperitoneal injections of 0.5 mmol/kg/d (0.1 mL 5% benzyl alcohol and 95% safflower oil solution) and control mice with vehicle only, once daily for 5 days per week over a duration of 4 weeks (n=8 mice per treatment). Statistical significance between Abiraterone and vehicle treatment groups is assessed by ANOVA based on a mixed-effect model.

[References]

[1]. Stein MN, et al. Androgen synthesis inhibitors in the treatment of castration-resistant prostate cancer. Asian J Androl. 2014 May-Jun;16(3):387-400.

[2]. Richards J, et al. Interactions of abiraterone, eplerenone, and prednisolone with wild-type and mutant androgen receptor: a rationale for increasing abiraterone exposure or combining with MDV3100. Cancer Res. 2012 May 1;72(9):2176-82.

[3]. Li R, 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.

[4]. Lee GT, et al. Intracrine androgen biosynthesis in renal cell carcinoma. Br J Cancer. 2017 Mar 28;116(7):937-943.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.1±0.1 g/cm3

[ Boiling Point ]:
506.7±50.0 °C at 760 mmHg

[ Melting Point ]:
127-130°C

[ Molecular Formula ]:
C₂₆H₃₃NO₂

[ Molecular Weight ]:
391.546

[ Flash Point ]:
260.2±30.1 °C

[ Exact Mass ]:
391.251129

[ PSA ]:
39.19000

[ LogP ]:
6.55

[ Vapour Pressure ]:
0.0±1.3 mmHg at 25°C

[ Index of Refraction ]:
1.584

[ Storage condition ]:
-20°C Freezer

Safety Information

[ Symbol ]:

GHS08

[ Signal Word ]:
Danger

[ Hazard Statements ]:
H360-H372

[ Precautionary Statements ]:
P201-P260-P280-P308 + P313

[ Target Organs ]:
Endocrine system

[ Hazard Codes ]:
Xi

[ RIDADR ]:
NONH for all modes of transport

[ RTECS ]:
BV7992100

[ HS Code ]:
2933399090

Precursor & DownStream

Precursor

DownStream

Customs

[ HS Code ]: 2933399090

[ Summary ]:
2933399090. other compounds containing an unfused pyridine ring (whether or not hydrogenated) in the structure. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

Articles

Phase I clinical trial of the CYP17 inhibitor abiraterone acetate demonstrating clinical activity in patients with castration-resistant prostate cancer who received prior ketoconazole therapy.

J. Clin. Oncol. 28(9) , 1481-8, (2010)

Abiraterone acetate is a prodrug of abiraterone, a selective inhibitor of CYP17, the enzyme catalyst for two essential steps in androgen biosynthesis. In castration-resistant prostate cancers (CRPCs),...

Significant and sustained antitumor activity in post-docetaxel, castration-resistant prostate cancer with the CYP17 inhibitor abiraterone acetate.

J. Clin. Oncol. 28(9) , 1489-95, (2010)

The principal objective of this trial was to evaluate the antitumor activity of abiraterone acetate, an oral, specific, irreversible inhibitor of CYP17 in docetaxel-treated patients with castration-re...

Phase II multicenter study of abiraterone acetate plus prednisone therapy in patients with docetaxel-treated castration-resistant prostate cancer.

J. Clin. Oncol. 28(9) , 1496-501, (2010)

Persistence of ligand-mediated androgen receptor signaling has been documented in castration-resistant prostate cancers (CRPCs). Abiraterone acetate (AA) is a potent and selective inhibitor of CYP17, ...

Related Compounds

The content on this webpage is sourced from various professional data sources. If you have any questions or concerns regarding the content, please feel free to contact service1@chemsrc.com.