PharmGKB: The Pharmacogenomics Knowledge Base

Drug/Small Molecule:
anastrozole

2D structure

Overview

Generic Names: Anastrozol; anastrozole
Trade Names: Anastrole; Arimidex
PharmGKB Accession Id: PA448432

Description

Anastrozole is a drug indicated in the treatment of breast cancer in post-menopausal women. It is used both in adjuvant therapy (i.e. following surgery) and in metastatic breast cancer. It decreases the amount of estrogens that the body makes. Anastrozole belongs in the class of drugs known as aromatase inhibitors. It inhibits the enzyme aromatase, which is responsible for converting androgens (produced by women in the adrenal glands) to estrogens. (source: Drug Bank)

Indication

For treatment of breast cancer in post-menopausal women. (source: Drug Bank)

ATC Therapeutic Category

  • L02BG:Enzyme inhibitors

Pharmacology, Interactions, and Contraindications

Mechanism Of Action

Anastrozole selectively inhibits aromatase. The principal source of circulating estrogen (primarily estradiol) is conversion of adrenally-generated androstenedione to estrone by aromatase in peripheral tissues. Therefore, aromatase inhibition leads to a decrease in circulatin estrogen, leading to a decreased tumor mass or delayed progression of tumor growth in some women. (source: Drug Bank)

Pharmacology

Anastrozole is a potent and selective non-steroidal aromatase inhibitor indicated for the treatment of advanced breast cancer in post-menopausal women with disease progression following tamoxifen therapy. Many breast cancers have estrogen receptors and growth of these tumors can be stimulated by estrogens. In post-menopausal women, the principal source of circulating estrogen (primarily estradiol) is conversion of adrenally-generated androstenedione to estrone by aromatase in peripheral tissues, such as adipose tissue, with further conversion of estrone to estradiol. Many breast cancers also contain aromatase; the importance of tumor-generated estrogens is uncertain. Treatment of breast cancer has included efforts to decrease estrogen levels by ovariectomy premenopausally and by use of anti-estrogens and progestational agents both pre- and post-menopausally, and these interventions lead to decreased tumor mass or delayed progression of tumor growth in some women. Anastrozole is a potent and selective non-steroidal aromatase inhibitor. It significantly lowers serum estradiol concentrations and has no detectable effect on formation of adrenal corticosteroids or aldosterone. (source: Drug Bank)

Food Interactions

Food decreases the rate of absorption, but the extent of absorption is not affected. (source: Drug Bank)

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Hepatic. Metabolized mainly by N-dealkylation, hydroxylation, and glucuronidation to inactive metabolites. Primary metabolite is an inactive triazole. (source: Drug Bank)

Protein Binding

40% (source: Drug Bank)

Absorption

Well absorbed into the systemic cirulation following oral administration. Food does not affect the extent of absorption. (source: Drug Bank)

Toxicity

In rats, lethality is greater than 100 mg/kg. (source: Drug Bank)

Isomeric SMILES Code:

CC(C)(C#N)c1cc(cc(c1)C(C)(C)C#N)Cn2cncn2 (source: Drug Bank)

Curated Annotations (Curated Annotation)

  1. rs6493497 at chr15:49418127 in CYP19A1
    Phenotype: This SNP, along with a second one in tight LD (rs71760050) was significantly associated, in a cohort of estrogen-receptor-positive patients with primary breast cancer larger than 3 cm, with change in aromatase activity before and after aromatase inhibitor neoadjuvant treatment . It was also associated, but not significantly so after adjustment for multiple testing, with change in estrone level and with pretreatment aromatase level. Study size: 45. Study population/ethnicity: Edinburgh female ER-positive patients, primary breast cancer larger than 3 cm. Significance metric(s): nominal p = 0.0063, p = 0.039 after adjustment for multiple testing. Type of association: PD; GN;FA. Second Phenotype: In a group of 200 women with early-stage breast cancer, who were treated with 1 mg/day adjuvant anastrozole, this SNP was significantly associated with pre-drug and post-drug estradiol plasma concentrations after adjusting for plasma anastrozole concentrations. Study size: 200. Study population: women with early-stage breast cancer (Mayo Clinic-M.D. Anderson pharmacogenomic study participants) . Significance metric(s):pre-drug p = 0.028; post-drug p = 0.0002. Type of association: PD; GN;FA
    Related Drugs:
    anastrozole, exemestane, letrozole
    Related Diseases:
    Breast Neoplasms
    Evidence:
    PMID:20048079
  2. rs7176005 at chr15:49418571 in CYP19A1
    Phenotype: This SNP, along with a second one in tight LD (rs6493497) was significantly associated, in a cohort of estrogen-receptor-positive patients with primary breast cancer larger than 3 cm, with change in aromatase activity before and after aromatase inhibitor neoadjuvant treatment . It was also associated, but not significantly so after adjustment for multiple testing, with change in estrone level and with pretreatment aromatase level. Study size: 45. Study population/ethnicity: Edinburgh female ER-positive patients, primary breast cancer larger than 3 cm. Significance metric(s): nominal p = 0.0063, p = 0.039 after adjustment for multiple testing. Type of association: PD; GN;FA. Second Phenotype: In a group of 200 women with early stage breast cancer, who were treated with 1 mg/day adjuvant anastrozole, this SNP was significantly associated with pre-drug and post-drug estradiol plasma concentrations after adjusting for plasma anastrozole concentrations. Study size: 200. Study population: women with early stage breast cancer (Mayo Clinic-M.D. Anderson pharmacogenomic study participants) . Significance metric(s):pre-drug p = 0.057; post-drug p = 0.0002. Type of association: PD; GN;FA
    Related Drugs:
    anastrozole, exemestane, letrozole
    Related Diseases:
    Breast Neoplasms
    Evidence:
    PMID:20048079
Variant names are different names that have been used in the literature and other resources to refer to the same variant.

The following genes are in curated knowledge about this drug.

  Gene Relationship Evidence
No phenotype data Genotype Data Available Literature annotations available Not annotated
CYP19A1
  • CO
  • PD
  • PK
  • FA
  • GN
Publications, Variants

A list of non-curated publications that mention this drug along with other genes is available.

Drug Targets

Gene Description
CYP19A1 Uncurated Annotation (source: Drug Bank)

The following drugs are in curated knowledge about this drug.

  Drug Relationship Evidence
No phenotype data No genotype data Literature annotations available Not annotated
conjugated estrogens
  •   
  • PD
  • PK
  •   
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
estradiol
  •   
  • PD
  • PK
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
estrone
  •   
  • PD
  • PK
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
tamoxifen
  •   
  •   
  • PK
  •   
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
testosterone
  •   
  • PD
  • PK
  •   
  •   
Publications

A list of non-curated publications that mention this drug along with other drugs is available.

Curated Information

The following diseases are in curated knowledge about this drug.

  Disease Relationship Evidence
Phenotype data available Genotype Data Available Literature annotations available Not annotated
Breast Neoplasms
  • CO
  • PD
  • PK
  • FA
  • GN
Publications, Variants
Phenotype data available Genotype Data Available Literature annotations available Not annotated
Neoplasms
  • CO
  •   
  •   
  •   
  •   
Publications

Non-Curated Information

A list of non-curated publications that mention this drug along with other diseases is available.

LinkOuts

Web Resource:
Wikipedia
DrugBank:
DB01217
KEGG Compound ID:
C08159
KEGG Drug ID:
D00960
PubChem Compound ID:
2187
PubChem Substance ID:
196979

Common Searches

Search PubMed
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Non-Curated Publications

A list of non-curated publications that mention this drug is available.

PharmGKB integrates drug information from different sources: DrugBank, Open Eye Scientific Software.
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