Abiraterone
[CAS# 154229-19-3]

Identification

• Classification: Biochemical >> Inhibitor >> Metabolism >> P450 (e.g. CYP17) inhibitor
• Name: Abiraterone
• Synonyms: 17-(3-Pyridyl)androsta-5,16-dien-3beta-ol
• Molecular Formula: C₂₄H₃₁NO
• Molecular Weight: 349.51
• CAS Registry Number: 154229-19-3
• EC Number: 810-941-6
• SMILES: C[C@]12CC[C@@H](CC1=CC[C@@H]3[C@@H]2CC[C@]4([C@H]3CC=C4C5=CN=CC=C5)C)O

Properties

• Density: 1.1±0.1 g/cm³ Calc.^*
• Boiling point: 500.2±50.0 ºC 760 mmHg (Calc.)^*
• Flash point: 256.3±30.1 ºC (Calc.)^*
• Solubility: DMSO 20 mg/mL, Water <1 mg/mL (Expl.)
• Index of refraction: 1.606 (Calc.)^*

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

Safety Data

• Hazard Symbols: GHS08;GHS09 Danger
• Hazard Statements: H360-H360F-H361-H361fd-H373-H400-H410
• Precautionary Statements: P203-P260-P273-P280-P318-P319-P391-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
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.	2	H361

Discovory and Applicatios

Abiraterone is a synthetic steroidal compound that functions as a potent and selective inhibitor of cytochrome P450 17A1 (CYP17A1), an enzyme essential for androgen biosynthesis. It is the active form of the prodrug abiraterone acetate, which is commonly administered orally to enhance bioavailability and systemic absorption. Abiraterone was developed to address the limitations of conventional androgen deprivation therapies in the treatment of castration-resistant prostate cancer (CRPC), a condition in which tumors continue to progress despite low circulating testosterone levels.

The discovery of abiraterone was based on medicinal chemistry efforts to identify molecules capable of inhibiting both 17α-hydroxylase and 17,20-lyase activities of CYP17A1. These enzymatic steps are crucial in the synthesis of testosterone and dihydrotestosterone, which drive the growth of androgen receptor-positive prostate cancer cells. By selectively targeting CYP17A1, abiraterone suppresses androgen production in the testes, adrenal glands, and tumor tissue, effectively reducing the hormonal stimulation that supports cancer progression.

Upon administration, abiraterone is generated from the hydrolysis of abiraterone acetate by esterases in the gastrointestinal tract and plasma. The active compound binds to the heme moiety of CYP17A1, inhibiting its catalytic activity and leading to a significant decrease in circulating androgens. This mechanism of action distinguishes abiraterone from earlier therapies that primarily targeted testicular androgen production, providing a more comprehensive suppression of androgen signaling in CRPC.

Clinically, abiraterone has been extensively used to treat metastatic CRPC, both in chemotherapy-naïve patients and those who have previously received docetaxel. It has been shown to prolong overall survival, delay disease progression, and improve patient quality of life. Abiraterone therapy is typically combined with low-dose corticosteroids such as prednisone to counteract the mineralocorticoid excess resulting from upstream steroid accumulation caused by CYP17A1 inhibition.

The structural design of abiraterone is based on the steroid nucleus, maintaining the 3-keto-17β-hydroxy configuration necessary for enzyme binding. Medicinal chemistry optimization focused on enhancing selectivity for CYP17A1 over other cytochrome P450 enzymes, reducing off-target effects, and ensuring metabolic stability. Its development exemplifies rational drug design targeting steroidogenic pathways, highlighting the importance of selective enzyme inhibition in therapeutic applications.

Beyond its direct clinical use, abiraterone has contributed to research on androgen receptor signaling and resistance mechanisms in prostate cancer. Studies on tumor adaptation to abiraterone treatment, such as the emergence of androgen receptor splice variants, have informed the development of combination therapies and next-generation inhibitors. The compound also serves as a model for designing selective inhibitors of steroidogenic enzymes in other endocrine disorders.

In summary, abiraterone is a CYP17A1 inhibitor that suppresses androgen biosynthesis and plays a critical role in the management of castration-resistant prostate cancer. Its discovery and development underscore the value of targeted enzyme inhibition, prodrug strategies, and structure-based medicinal chemistry in creating effective therapies for hormone-dependent cancers.