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targets (1) enzymes (4)
for drugs
Identification
Name Anastrozole
Accession Number DB01217 (APRD00016)
Type small molecule
Groups approved
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.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Anastrozol
  • anastrozole
Brand names
  • Anastrole
  • Arimidex
Brand name mixtures Not Available
Categories
  • Antineoplastic Agents
  • Antineoplastic Agents, Hormonal
  • Aromatase Inhibitors
CAS number 120511-73-1
Weight Average: 293.3663
Monoisotopic: 293.164045633
Chemical Formula C17H19N5
InChI Key InChIKey=YBBLVLTVTVSKRW-UHFFFAOYSA-N
InChI
InChI=1S/C17H19N5/c1-16(2,9-18)14-5-13(8-22-12-20-11-21-22)6-15(7-14)17(3,4)10-19/h5-7,11-12H,8H2,1-4H3
Plain Text
IUPAC Name
2-[3-(1-cyano-1-methylethyl)-5-(1H-1,2,4-triazol-1-ylmethyl)phenyl]-2-methylpropanenitrile
SMILES
CC(C)(C#N)C1=CC(=CC(CN2C=NC=N2)=C1)C(C)(C)C#N
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Cumenes and Derivatives
Substructures
  • Triazoles
  • Nitriles and Derivatives
  • Benzene and Derivatives
  • Cumenes and Derivatives
  • Cyanides
  • Heterocyclic compounds
  • Aromatic compounds
  • Cyanamides
Pharmacology
Indication For adjuvant treatment of hormone receptor positive breast cancer , as well as hormonal treatment of advanced breast cancer in post-menopausal women. Has also been used to treat pubertal gynecomastia and McCune-Albright syndrome; however, manufacturer states that efficacy for these indications have not been established.
Pharmacodynamics 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.
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 serum and tumor concentration of estrogen, leading to a decreased tumor mass or delayed progression of tumor growth in some women. Anastrozole has no detectable effect on synthesis of adrenal corticosteroids, aldosterone, and thyroid hormone.
Absorption Rapidly absorbed into the systemic cirulation following oral administration. Peak plasma concentrations are usually attained within 2 hours under fasting conditions, with steady-state plasma concentrations attained in approximately 7 days.
Volume of distribution Not Available
Protein binding 40%
Metabolism

Hepatic. Metabolized mainly by N-dealkylation, hydroxylation, and glucuronidation to inactive metabolites. Primary metabolite is an inactive triazole.
Route of elimination Hepatic metabolism accounts for approximately 85% of anastrozole elimination. Renal elimination accounts for approximately 10% of total clearance.
Half life 50 hours
Clearance Not Available
Toxicity In rats, lethality is greater than 100 mg/kg.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Accord healthcare inc usa
  • Dr reddys laboratories ltd
  • Fresenius kabi oncology plc
  • Mylan pharmaceuticals inc
  • Natco pharma ltd
  • Roxane laboratories inc
  • Sandoz inc
  • Stason pharmaceuticals inc
  • Synthon pharmaceuticals inc
  • Teva pharmaceuticals usa
  • Three rivers pharmaceuticals llc
  • Watson laboratories
  • Zydus pharmaceuticals usa inc
  • Astrazeneca uk ltd
  • AstraZeneca Pharmaceuticals
Packagers
Dosage forms
Form Route Strength
Tablet Oral
Prices
Unit description Cost Unit
Anastrozole 100% powder 1326.52 USD g
Arimidex 1 mg tablet 15.3 USD tablet
Aromasin 25 mg tablet 14.04 USD tablet
Patents
Country Patent Number Approved Expires
United States RE36617 1993-06-27 2010-06-27
Canada 1337420 1995-10-24 2012-10-24
Properties
State solid
Melting point 130.14 oC
Experimental Properties
Property Value Source
water solubility 0.5 mg/mL PhysProp
logP 2.4 PhysProp
Predicted Properties
Property Value Source
water solubility 6.61e-02 g/l ALOGPS
logP 2.31 ALOGPS
logP 3.03 ChemAxon Molconvert
logS -3.65 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 4 ChemAxon Molconvert
hydrogen donor count 0 ChemAxon Molconvert
polar surface area 78.29 ChemAxon Molconvert
rotatable bond count 4 ChemAxon Molconvert
refractivity 97.47 ChemAxon Molconvert
polarizability 31.97 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  1. Howell A, Cuzick J, Baum M, Buzdar A, Dowsett M, Forbes JF, Hoctin-Boes G, Houghton J, Locker GY, Tobias JS: Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years’ adjuvant treatment for breast cancer. Lancet. 2005 Jan 1-7;365(9453):60-2. Pubmed
  2. Mauras N, Bishop K, Merinbaum D, Emeribe U, Agbo F, Lowe E: Pharmacokinetics and pharmacodynamics of anastrozole in pubertal boys with recent-onset gynecomastia. J Clin Endocrinol Metab. 2009 Aug;94(8):2975-8. Epub 2009 May 26. Pubmed
  3. Nabholtz JM: Role of anastrozole across the breast cancer continuum: from advanced to early disease and prevention. Oncology. 2006;70(1):1-12. Epub 2006 Jan 26. Pubmed
  4. Milani M, Jha G, Potter DA: Anastrozole Use in Early Stage Breast Cancer of Post-Menopausal Women. Clin Med Ther. 2009 Mar 31;1:141-156. Pubmed
  5. Gangadhara S, Bertelli G: Long-term efficacy and safety of anastrozole for adjuvant treatment of early breast cancer in postmenopausal women. Ther Clin Risk Manag. 2009 Aug;5(4):291-300. Epub 2009 May 4. Pubmed
  6. Santen RJ, Brodie H, Simpson ER, Siiteri PK, Brodie A: History of aromatase: saga of an important biological mediator and therapeutic target. Endocr Rev. 2009 Jun;30(4):343-75. Epub 2009 Apr 23. Pubmed
External Links
Resource Link
KEGG Drug D00960 Link_out
KEGG Compound C08159 Link_out
PubChem Compound 2187 Link_out
PubChem Substance 46504987 Link_out
ChemSpider 2102 Link_out
BindingDB 10015 Link_out
ChEBI 2704 Link_out
ChEMBL 2704 Link_out
Therapeutic Targets Database DAP000627 Link_out
PharmGKB PA448432 Link_out
Drug Product Database 2224135 Link_out
RxList http://www.rxlist.com/cgi/generic2/anastr.htm Link_out
Drugs.com http://www.drugs.com/cdi/anastrozole.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/ari1028.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Anastrozole Link_out
ATC Codes
  • L02BG03
AHFS Codes
  • 10:00.00
PDB Entries Not Available
FDA label show (258 KB)
MSDS show (57.3 KB)
Interactions
Drug Interactions
Drug Interaction
Food Interactions
  • Food decreases the rate of absorption, but the extent of absorption is not affected.
Targets

1. Cytochrome P450 19A1

Pharmacological action: yes
Actions: inhibitor

Catalyzes the formation of aromatic C18 estrogens from C19 androgens

Organism class: human
UniProt ID: P11511 Link_out
Gene: CYP19A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Mauras N, Bishop K, Merinbaum D, Emeribe U, Agbo F, Lowe E: Pharmacokinetics and pharmacodynamics of anastrozole in pubertal boys with recent-onset gynecomastia. J Clin Endocrinol Metab. 2009 Aug;94(8):2975-8. Epub 2009 May 26. Pubmed
  3. Nabholtz JM: Role of anastrozole across the breast cancer continuum: from advanced to early disease and prevention. Oncology. 2006;70(1):1-12. Epub 2006 Jan 26. Pubmed
  4. Jakesz R, Greil R, Gnant M, Schmid M, Kwasny W, Kubista E, Mlineritsch B, Tausch C, Stierer M, Hofbauer F, Renner K, Dadak C, Rucklinger E, Samonigg H: Extended adjuvant therapy with anastrozole among postmenopausal breast cancer patients: results from the randomized Austrian Breast and Colorectal Cancer Study Group Trial 6a. J Natl Cancer Inst. 2007 Dec 19;99(24):1845-53. Epub 2007 Dec 11. Pubmed
  5. Cuzick J: Anastrozole. Drugs Today (Barc). 2005 Apr;41(4):227-39. Pubmed
  6. Rugo HS: The breast cancer continuum in hormone-receptor-positive breast cancer in postmenopausal women: evolving management options focusing on aromatase inhibitors. Ann Oncol. 2008 Jan;19(1):16-27. Epub 2007 Aug 9. Pubmed
  7. Milani M, Jha G, Potter DA: Anastrozole Use in Early Stage Breast Cancer of Post-Menopausal Women. Clin Med Ther. 2009 Mar 31;1:141-156. Pubmed
  8. Gangadhara S, Bertelli G: Long-term efficacy and safety of anastrozole for adjuvant treatment of early breast cancer in postmenopausal women. Ther Clin Risk Manag. 2009 Aug;5(4):291-300. Epub 2009 May 4. Pubmed
  9. Santen RJ, Brodie H, Simpson ER, Siiteri PK, Brodie A: History of aromatase: saga of an important biological mediator and therapeutic target. Endocr Rev. 2009 Jun;30(4):343-75. Epub 2009 Apr 23. Pubmed
Enzymes

1. Cytochrome P450 19A1

Actions: inhibitor

Catalyzes the formation of aromatic C18 estrogens from C19 androgens

UniProt ID: P11511 Link_out
Gene: CYP19A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 1A2

Actions: inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen

UniProt ID: P05177 Link_out
Gene: CYP1A2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

3. Cytochrome P450 2C9

Actions: inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S- warfarin, diclofenac, phenytoin, tolbutamide and losartan

UniProt ID: P11712 Link_out
Gene: CYP2C9
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

4. Cytochrome P450 3A4

Actions: inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on April 19, 2011 15:09

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.