Abiraterone acetate
[CAS# 154229-18-2]

Identification

• Classification: Organic raw materials >> Carboxylic compounds and derivatives >> Carboxylic esters and their derivatives
• Name: Abiraterone acetate
• Synonyms: [(3S,8R,9S,10R,13S,14S)-10,13-dimethyl-17-pyridin-3-yl-2,3,4,7,8,9,11,12,14,15-decahydro-1H-cyclopenta[a]phenanthren-3-yl] acetate
• Molecular Formula: C₂₆H₃₃NO₂
• Molecular Weight: 391.55
• CAS Registry Number: 154229-18-2
• EC Number: 620-314-7
• SMILES: CC(=O)O[C@H]1CC[C@@]2([C@H]3CC[C@]4([C@H]([C@@H]3CC=C2C1)CC=C4C5=CN=CC=C5)C)C

Properties

• Boiling point: 506.7±50.0 °C 760 mmHg (Calc.)^*
• Flash point: 260.2±30.1 °C (Calc.)^*
• Solubility: DMSO 100 mg/mL, Water $lessThan$1 mg/mL (Expl.)
• Index of refraction: 1.584 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07;GHS08;GHS09 Danger
• Risk Statements: H302-H360-H361-H373-H400-H410
• Safety Statements: P203-P260-P264-P270-P273-P280-P301+P317-P318-P319-P330-P391-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Reproductive toxicity	Repr.	2	H361
Acute toxicity	Acute Tox.	4	H302
Specific target organ toxicity - repeated exposure	STOT RE	2	H373
Chronic hazardous to the aquatic environment	Aquatic Chronic	1	H410
Reproductive toxicity	Repr.	1B	H360
Acute hazardous to the aquatic environment	Aquatic Acute	1	H400
Reproductive toxicity	Repr.	1B	H360FD
Specific target organ toxicity - repeated exposure	STOT RE	1	H372
Reproductive toxicity	Repr.	1A	H360
Skin irritation	Skin Irrit.	2	H315
Acute toxicity	Acute Tox.	4	H332

Discovery and Applications

Abiraterone acetate is a synthetic steroidal compound that functions as a selective inhibitor of cytochrome P450 17A1 (CYP17A1), a critical enzyme in androgen biosynthesis. It is the acetate ester prodrug of abiraterone, which enhances oral bioavailability and facilitates systemic absorption. The discovery of abiraterone acetate was motivated by the need for more effective therapies for castration-resistant prostate cancer (CRPC), a form of prostate cancer that continues to progress despite androgen deprivation therapy.

The compound was developed through targeted medicinal chemistry efforts to inhibit androgen production at multiple sites, including the testes, adrenal glands, and tumor tissue. CYP17A1 catalyzes both 17α-hydroxylase and 17,20-lyase reactions, which are essential for the biosynthesis of testosterone and dihydrotestosterone. By selectively inhibiting CYP17A1, abiraterone acetate effectively reduces androgen levels, thereby limiting the stimulation of androgen receptor-positive prostate cancer cells.

Upon oral administration, abiraterone acetate is rapidly hydrolyzed by esterases to generate the active form, abiraterone. Abiraterone binds to the active site of CYP17A1, blocking its enzymatic activity and reducing androgen production. This mechanism results in decreased serum testosterone levels and suppression of androgen-driven tumor growth. The ability of abiraterone acetate to inhibit extragonadal androgen synthesis distinguishes it from earlier therapies and contributes to its clinical efficacy in advanced prostate cancer.

Abiraterone acetate has been extensively applied in the treatment of metastatic CRPC, both in chemotherapy-naïve patients and those previously treated with docetaxel. Clinical studies have demonstrated that it prolongs overall survival, delays disease progression, and improves quality of life. It is typically administered in combination with prednisone to mitigate mineralocorticoid excess, a side effect resulting from upstream accumulation of steroid precursors due to CYP17A1 inhibition.

The synthesis of abiraterone acetate involves modification of the steroid nucleus, particularly at the C3 position, to introduce the acetate ester group. The structural design retains the 17β-hydroxy-3-keto configuration, which is essential for enzyme recognition and inhibition. Optimization of the steroid scaffold has been crucial to achieving selectivity for CYP17A1 over other cytochrome P450 enzymes, minimizing off-target effects and toxicity.

Beyond its therapeutic application, abiraterone acetate has provided a framework for understanding steroidogenesis inhibition in prostate cancer treatment. It has spurred research into resistance mechanisms, such as upregulation of androgen receptor splice variants, and has encouraged the development of combination therapies to overcome clinical resistance. The compound is also used as a model for designing other selective steroidogenesis inhibitors for endocrine-related diseases.

In addition to oncology, abiraterone acetate has contributed to the broader field of medicinal chemistry, exemplifying the utility of prodrugs, selective enzyme targeting, and rational drug design in addressing unmet clinical needs. Its development underscores the importance of structure-based approaches and pharmacokinetic optimization in creating therapeutically effective and safe compounds for complex diseases like prostate cancer.