Anastrozole (T3D4796)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (2)XML
Targets (2)
Record Information
Version2.0
Creation Date2014-09-11 05:17:00 UTC
Update Date2014-12-24 20:26:57 UTC
Accession NumberT3D4796
Identification
Common NameAnastrozole
ClassSmall Molecule
DescriptionAnastrozole 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.
Compound Type
  • Amine
  • Antineoplastic Agent, Hormonal
  • Aromatase Inhibitor
  • Drug
  • Metabolite
  • Nitrile
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
alpha,alpha,Alpha',alpha'-tetramethyl-5-(1H-1,2,4-triazol-1-ylmethyl)-m-benzenediacetonitrile
Anastrole
Anastrozol
Arimidex
Chemical FormulaC17H19N5
Average Molecular Mass293.366 g/mol
Monoisotopic Mass293.164 g/mol
CAS Registry Number120511-73-1
IUPAC Name2-[3-(1-cyano-1-methylethyl)-5-(1H-1,2,4-triazol-1-ylmethyl)phenyl]-2-methylpropanenitrile
Traditional Nameanastrozole
SMILESCC(C)(C#N)C1=CC(=CC(CN2C=NC=N2)=C1)C(C)(C)C#N
InChI IdentifierInChI=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 KeyInChIKey=YBBLVLTVTVSKRW-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as phenylpropanes. These are organic compounds containing a phenylpropane moiety.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassPhenylpropanes
Direct ParentPhenylpropanes
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 FrameworkAromatic heteromonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point130.14°C
Boiling PointNot Available
Solubility0.5 mg/mL
LogP2.4
Predicted Properties
PropertyValueSource
Water Solubility0.066 g/LALOGPS
logP2.31ALOGPS
logP3.03ChemAxon
logS-3.6ALOGPS
pKa (Strongest Basic)2.25ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area78.29 ŲChemAxon
Rotatable Bond Count4ChemAxon
Refractivity97.47 m³·mol⁻¹ChemAxon
Polarizability31.97 ųChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-004i-3290000000-ff4ef0855ebb4330d2d22016-09-22View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-004l-1390000000-8636c0aef7d79b8053282017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-004l-1390000000-8636c0aef7d79b8053282017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-004l-0190000000-739ac0c546bb150b1c602017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-004i-0090000000-8ccdc5fa9f18334eae922017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 20V, Positivesplash10-03k9-0970000000-631de023e85e74dc9b972021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 35V, Positivesplash10-004i-0090000000-da446dd012935939477a2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 60V, Positivesplash10-004i-0290000000-68b444c53777d3d517492021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 90V, Positivesplash10-00kf-0910000000-40a907f3bc5fa1999ffd2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 30V, Positivesplash10-00e9-0900000000-55004c246dccb53413bb2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 10V, Positivesplash10-03k9-0980000000-71cd7bb463fca110eeab2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 35V, Positivesplash10-004i-0290000000-2b885de3e2d4dc88aa812021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 40V, Positivesplash10-00e9-0900000000-5113a05488a50bd3517c2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 50V, Positivesplash10-01b9-0900000000-908023356faf6f180af32021-09-20View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0006-0090000000-84795d1e4c8cdc8517aa2016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0006-0090000000-6a08f214a3b45616d2f42016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-006x-2390000000-cad4b3339fe0a358312e2016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0006-0090000000-84795d1e4c8cdc8517aa2016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0006-0090000000-6a08f214a3b45616d2f42016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-006x-2390000000-cad4b3339fe0a358312e2016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0006-0090000000-84795d1e4c8cdc8517aa2016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0006-0090000000-6a08f214a3b45616d2f42016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-006x-2390000000-cad4b3339fe0a358312e2016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0006-0090000000-cca188a9698d9ce00e772016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0006-0090000000-7e154d941cb439c9f5a92016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-014r-5290000000-bd403a6901863274c5b72016-08-03View Spectrum
Toxicity Profile
Route of ExposureRapidly 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 ToxicityAnastrozole 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)
MetabolismHepatic. 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 ValuesIn rats, lethality is greater than 100 mg/kg.
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor 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 LevelNot Available
Health EffectsNot Available
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB01217
HMDB IDHMDB15348
PubChem Compound ID2187
ChEMBL IDCHEMBL1399
ChemSpider ID2102
KEGG IDC08159
UniProt IDNot Available
OMIM ID
ChEBI ID2704
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkAnastrozole
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.

MSDSLink
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. [15639680 ]
  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. doi: 10.1210/jc.2008-2527. Epub 2009 May 26. [19470631 ]
  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. [16439860 ]
  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. [19794821 ]
  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. [19753124 ]
  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. doi: 10.1210/er.2008-0016. Epub 2009 Apr 23. [19389994 ]
  7. Wikipedia. Cyanide poisoning. Last Updated 30 March 2009. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. Aromatase
General Function:
Oxygen binding
Specific Function:
Catalyzes the formation of aromatic C18 estrogens from C19 androgens.
Gene Name:
CYP19A1
Uniprot ID:
P11511
Molecular Weight:
57882.48 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC500.737 uMNVS_ADME_hCYP19A1Novascreen
AC500.152 uMTox21_Aromatase_InhibitionTox21/NCGC
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
Target Details
2. Estrogen receptor
General Function:
Zinc ion binding
Specific Function:
Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Isoform 3 is involved in activation of NOS3 and endothelial nitric oxide production. Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full length receptor. Essential for MTA1-mediated transcriptional regulation of BRCA1 and BCAS3. Isoform 3 can bind to ERE and inhibit isoform 1.
Gene Name:
ESR1
Uniprot ID:
P03372
Molecular Weight:
66215.45 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC506.68 uMACEA_T47D_80hr_PositiveACEA Biosciences
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]