SynCED: Anastrozole

Record Information

Version

1.0

Creation Date

2014-09-11 05:17:00 UTC

Update Date

2026-08-19 20:19:01 UTC

Accession Number

CHEM003753

Identification

Common Name

Anastrozole

Class

Small Molecule

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.

Contaminant Sources

Disinfection Byproducts
EAFUS Chemicals
HMDB Contaminants - Urine
HPV EPA Chemicals
My Exposome Chemicals
OECD HPV Chemicals
STOFF IDENT Compounds
Suspected Compounds – Schymanski Project
T3DB toxins
ToxCast & Tox21 Chemicals

Contaminant Type

Amine
Antineoplastic Agent, Hormonal
Aromatase Inhibitor
Drug
Human Neurotoxin
Metabolite
Nitrile
Organic Compound
Synthetic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Value	Source
Arimidex	Kegg
alpha,alpha,Alpha',alpha'-tetramethyl-5-(1H-1,2,4-triazol-1-ylmethyl)-m-benzenediacetonitrile	HMDB
Anastrozol	HMDB
a,a,Alpha',alpha'-tetramethyl-5-(1H-1,2,4-triazol-1-ylmethyl)-m-benzenediacetonitrile	HMDB
Α,α,alpha',alpha'-tetramethyl-5-(1H-1,2,4-triazol-1-ylmethyl)-m-benzenediacetonitrile	HMDB
AstraZeneca brand OF anastrozole	HMDB
ICI D1033	HMDB
Zeneca brand OF anastrozole	HMDB
Zeneca ZD 1033	HMDB
2,2'-(5-(1H-1,2,4-Triazol-1-ylmethyl)-1,3-phenylene)bis(2-methylpropionitrile)	HMDB
Astra brand OF anastrozole	HMDB
Anastrazole	HMDB

Chemical Formula

C₁₇H₁₉N₅

Average Molecular Mass

293.366 g/mol

Monoisotopic Mass

293.164 g/mol

CAS Registry Number

120511-73-1

IUPAC Name

2-[3-(1-cyano-1-methylethyl)-5-(1H-1,2,4-triazol-1-ylmethyl)phenyl]-2-methylpropanenitrile

Traditional Name

anastrozole

SMILES

CC(C)(C#N)C1=CC(=CC(CN2C=NC=N2)=C1)C(C)(C)C#N

InChI Identifier

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

InChI Key

YBBLVLTVTVSKRW-UHFFFAOYSA-N

Chemical Taxonomy

Description

Belongs to the class of organic compounds known as phenylpropanes. These are organic compounds containing a phenylpropane moiety.

Kingdom

Organic compounds

Super Class

Benzenoids

Class

Benzene and substituted derivatives

Sub Class

Phenylpropanes

Direct Parent

Phenylpropanes

Alternative Parents

Substituents

Phenylpropane
Heteroaromatic compound
1,2,4-triazole
Azole
Azacycle
Organoheterocyclic compound
Nitrile
Carbonitrile
Organic nitrogen compound
Organopnictogen compound
Hydrocarbon derivative
Organonitrogen compound
Aromatic heteromonocyclic compound

Molecular Framework

Aromatic heteromonocyclic compounds

External Descriptors

nitrile (CHEBI:2704 )
triazoles (CHEBI:2704 )

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Membrane

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Not Available

Applications

Not Available

Biological Roles

Not Available

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	130.14°C
Boiling Point	Not Available
Solubility	0.5 mg/mL

Predicted Properties

Property	Value	Source
Water Solubility	0.066 g/L	ALOGPS
logP	2.31	ALOGPS
logP	3.03	ChemAxon
logS	-3.6	ALOGPS
pKa (Strongest Basic)	2.25	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	4	ChemAxon
Hydrogen Donor Count	0	ChemAxon
Polar Surface Area	78.29 Å²	ChemAxon
Rotatable Bond Count	4	ChemAxon
Refractivity	97.47 m³·mol⁻¹	ChemAxon
Polarizability	31.97 Å³	ChemAxon
Number of Rings	2	ChemAxon
Bioavailability	Yes	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	No	ChemAxon

Spectra

Toxicity Profile

Route of Exposure

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.

Mechanism of Toxicity

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. Organic nitriles decompose into cyanide ions both in vivo and in vitro. Consequently the primary mechanism of toxicity for organic nitriles is their production of toxic cyanide ions or hydrogen cyanide. Cyanide is an inhibitor of cytochrome c oxidase in the fourth complex of the electron transport chain (found in the membrane of the mitochondria of eukaryotic cells). It complexes with the ferric iron atom in this enzyme. The binding of cyanide to this cytochrome prevents transport of electrons from cytochrome c oxidase to oxygen. As a result, the electron transport chain is disrupted and the cell can no longer aerobically produce ATP for energy. Tissues that mainly depend on aerobic respiration, such as the central nervous system and the heart, are particularly affected. Cyanide is also known produce some of its toxic effects by binding to catalase, glutathione peroxidase, methemoglobin, hydroxocobalamin, phosphatase, tyrosinase, ascorbic acid oxidase, xanthine oxidase, succinic dehydrogenase, and Cu/Zn superoxide dismutase. Cyanide binds to the ferric ion of methemoglobin to form inactive cyanmethemoglobin. (7)

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

Toxicity Values

In rats, lethality is greater than 100 mg/kg.

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Uses/Sources

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.

Minimum Risk Level

Not Available

Health Effects

Not Available

Symptoms

Not Available

Treatment

Not Available

Concentrations

Status	Value	Unit	Sample Location	Reference

External Links

DrugBank ID

DB01217

HMDB ID

HMDB0015348

FooDB ID

Not Available

Phenol Explorer ID

Not Available

KNApSAcK ID

Not Available

BiGG ID

Not Available

BioCyc ID

Not Available

METLIN ID

Not Available

PDB ID

Not Available

Wikipedia Link

Chemspider ID

ChEBI ID

PubChem Compound ID

Kegg Compound ID

YMDB ID

ECMDB ID

Not Available

References

Synthesis Reference

Anil Khile, Narendra Joshi, Shekhar Bhirud, “Process for the preparation of anastrozole and intermediates thereof.” U.S. Patent US20060189670, issued August 24, 2006.

MSDS

Link

General References

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.

2. 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.

3. 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. doi: 10.1210/er.2008-0016. Epub 2009 Apr 23.

4. 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. doi: 10.1210/jc.2008-2527. Epub 2009 May 26.

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.

6. 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.

Anastrozole (CHEM003753)

Structure for CHEM003753: Anastrozole