Anastrozole
[CAS# 120511-73-1]

Identification

• Classification: API >> Antineoplastic agents >> Hormone antineoplastic agents
• Name: Anastrozole
• Synonyms: Tetramethyl-5-(1H-1,2,4-triazol-1ylmethyl) 1,3-benzenediacetionitrile
• Molecular Formula: C₁₇H₁₉N₅
• Molecular Weight: 293.37
• CAS Registry Number: 120511-73-1
• EC Number: 601-715-6
• SMILES: CC(C)(C#N)C1=CC(=CC(=C1)CN2C=NC=N2)C(C)(C)C#N

Properties

• Solubility: 100 mM (DMSO), 100mM (ethanaol) (Expl.)
• Density: 1.1±0.1 g/cm³, Calc.^*
• Melting point: 81-82 °C
• Index of Refraction: 1.580, Calc.^*
• Boiling Point: 469.7±55.0 °C (760 mmHg), Calc.^*
• Flash Point: 237.9±31.5 °C, Calc.^*

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

Safety Data

• Hazard Symbols: GHS06;GHS07;GHS08 Dander
• Risk Statements: H301-H302-H351-H360
• Safety Statements: P203-P264-P270-P280-P301+P316-P301+P317-P318-P321-P330-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Reproductive toxicity	Repr.	1B	H360
Acute toxicity	Acute Tox.	4	H302
Carcinogenicity	Carc.	2	H351
Acute toxicity	Acute Tox.	3	H301
Chronic hazardous to the aquatic environment	Aquatic Chronic	1	H410
Specific target organ toxicity - repeated exposure	STOT RE	1	H372
Acute toxicity	Acute Tox.	3	H331
Reproductive toxicity	Repr.	2	H361
Specific target organ toxicity - repeated exposure	STOT RE	2	H373
Germ cell mutagenicity	Muta.	2	H341
Acute toxicity	Acute Tox.	4	H332
Chronic hazardous to the aquatic environment	Aquatic Chronic	4	H413
Reproductive toxicity	Repr.	1B	H360FD

Discovery and Applications

Anastrozole, a nonsteroidal aromatase inhibitor, was developed in the early 1990s as a breakthrough treatment for hormone receptor-positive breast cancer. The need for more selective and effective therapies to manage estrogen-driven cancers led to its synthesis. Anastrozole specifically targets the aromatase enzyme, responsible for converting androgens into estrogens in postmenopausal women. By inhibiting this enzyme, anastrozole reduces estrogen levels, which is essential for slowing the growth of hormone-dependent tumors. Approved by the U.S. Food and Drug Administration (FDA) in 1995, it became a vital therapeutic option for postmenopausal women with early and advanced stages of breast cancer.

Anastrozole's mechanism of action involves reversible binding to the aromatase enzyme, preventing the conversion of testosterone and androstenedione to estradiol and estrone. This selective inhibition leads to a significant reduction in circulating estrogen levels, which is crucial since elevated estrogen levels promote the proliferation of estrogen receptor-positive (ER+) breast cancer cells. Anastrozole's specificity for aromatase ensures minimal interference with other steroidal pathways, resulting in fewer side effects compared to older treatments like tamoxifen. This targeted approach allows patients to tolerate the therapy more effectively while achieving better outcomes.

In clinical practice, anastrozole is widely used as an adjuvant therapy for early-stage breast cancer following surgery, chemotherapy, or radiation. It has demonstrated significant improvements in disease-free survival and a lower risk of cancer recurrence when compared to tamoxifen. The ATAC (Arimidex, Tamoxifen Alone or in Combination) trial, one of the most pivotal studies, highlighted anastrozole’s superiority over tamoxifen in terms of efficacy and safety. For advanced or metastatic breast cancer, anastrozole is often the first-line treatment for postmenopausal women, providing a non-invasive and effective alternative to chemotherapy.

Anastrozole is also being explored for other medical applications. In reproductive medicine, it has shown potential in the treatment of infertility caused by polycystic ovary syndrome (PCOS). By suppressing estrogen production, anastrozole can stimulate the pituitary gland to release follicle-stimulating hormone (FSH), promoting ovulation in women who do not respond to conventional fertility drugs like clomiphene citrate. Additionally, it has been investigated for use in reducing gynecomastia, a condition of breast tissue enlargement in men caused by an imbalance of estrogen and androgens.

Anastrozole's pharmacological benefits extend to potential applications in preventing breast cancer recurrence in high-risk patients. Studies have indicated that its use as a prophylactic treatment may reduce the incidence of breast cancer in postmenopausal women with elevated risk factors. Ongoing research into its long-term effects, safety profile, and combination with other targeted therapies continues to expand its therapeutic relevance.

The discovery and development of anastrozole represent a significant advancement in targeted cancer therapy, offering postmenopausal women with ER+ breast cancer an effective, safe, and well-tolerated option. Its role in oncology and potential applications in reproductive health highlight the compound's versatility and importance in medical science.

References

1998. Anastrozole: a new addition to the armamentarium against advanced breast cancer. American Journal of Clinical Oncology.
DOI: 10.1097/00000421-199804000-00014

2000. An overview of the use of non-steroidal aromatase inhibitors in the treatment of breast cancer. European Journal of Cancer.
DOI: 10.1016/s0959-8049(00)00238-0

2005. Exploratory study of drug plasma levels during bicalutamide 150 mg therapy co-administered with tamoxifen or anastrozole for prophylaxis of gynecomastia and breast pain in men with prostate cancer. Cancer Chemotherapy and Pharmacology.
DOI: 10.1007/s00280-005-1016-1