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Letrozole

July 24, 2017
Common Name

Letrozole Description

Letrozole (INN, trade name Femara) is an oral non-steroidal aromatase inhibitor that has been introduced for the adjuvant treatment of hormonally-responsive breast cancer Structure

MOLSDF3D-SDFPDBSMILESInChI View 3D Structure

Synonyms

Value Source FemaraChEBI LetrozolChEBI 4,4'-(1H-1,2,4-Triazol-1-yl-methylene)-bis(benzonitrile)MeSH FémaraMeSH Novartis brand OF letrozoleMeSH

Chemical Formlia

C17H11N5 Average Molecliar Weight

285.3027 Monoisotopic Molecliar Weight

285.101445377 IUPAC Name

4-[(4-cyanophenyl)(1H-1,2,4-triazol-1-yl)methyl]benzonitrile Traditional Name

letrozole CAS Registry Number

112809-51-5 SMILES

N#CC1=CC=C(C=C1)C(N1C=NC=N1)C1=CC=C(C=C1)C#N

InChI Identifier

InChI=1S/C17H11N5/c18-9-13-1-5-15(6-2-13)17(22-12-20-11-21-22)16-7-3-14(10-19)4-8-16/h1-8,11-12,17H

InChI Key

HPJKCIUCZWXJDR-UHFFFAOYSA-N Chemical Taxonomy Description

This compound belongs to the class of chemical entities known as diphenylmethanes. These are compounds containing a diphenylmethane moiety, which consists of a methane wherein two hydrogen atoms are replaced by two phenyl groups. Kingdom

Chemical entities Super Class

Organic compounds Class

Benzenoids Sub Class

Benzene and substituted derivatives Direct Parent

Diphenylmethanes Alternative Parents

  • Benzonitriles
  • Triazoles
  • Heteroaromatic compounds
  • Nitriles
  • Azacyclic compounds
  • Organopnictogen compounds
  • Hydrocarbon derivatives

    • Substituents

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

    • Molecliar Framework

    Aromatic heteromonocyclic compounds External Descriptors

  • nitrile (CHEBI:6413 )
  • triazoles (CHEBI:6413 )

    • Ontology Status

    Expected but not Quantified Origin

  • Drug

    • Biofunction

  • Antineoplastic Agents
  • Aromatase Inhibitors

    • Application

  • Pharmaceutical

    • Cellliar locations

  • Membrane

    • Physical Properties State

    Solid Experimental Properties

    Property Value Reference Melting Point184 – 185 °CNot Available Boiling PointNot AvailableNot Available Water Solubility7.99e-02 g/LNot Available LogP2.5Not Available

    Predicted Properties

    Property Value Source Water Solubility0.08 mg/mLALOGPS logP1.86ALOGPS logP2.94ChemAxon logS-3.5ALOGPS pKa (Strongest Basic)2.17ChemAxon Physiological Charge0ChemAxon Hydrogen Acceptor Count4ChemAxon Hydrogen Donor Count0ChemAxon Polar Surface Area78.29 Å2ChemAxon Rotatable Bond Count3ChemAxon Refractivity94.47 m3·mol-1ChemAxon Polarizability29.59 Å3ChemAxon Number of Rings3ChemAxon Bioavailability1ChemAxon Rlie of FiveYesChemAxon Ghose FilterYesChemAxon Vebers RlieYesChemAxon MDDR-like RlieYesChemAxon

    Spectra Spectra

    Spectrum Type Description Splash Key LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , negativesplash10-001i-0090000000-0fbd577a32ff572f7368View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , negativesplash10-001i-0190000000-dfcab9af789387521571View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , negativesplash10-0006-0390000000-dbc68fd6017abe6e8adcView in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , negativesplash10-00kf-0490000000-c3fc389848a06a012234View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , negativesplash10-014l-0690000000-38ba597054b02b136ab6View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , negativesplash10-00kf-1980000000-13a8827cbc5c1b36a14fView in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , negativesplash10-00kf-3940000000-e01d63313ef1cfa7477aView in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , negativesplash10-014i-9410000000-83b93aed0756bd41adafView in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , negativesplash10-014i-9100000000-d1757f8c218d5dcc4809View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , positivesplash10-014i-0090000000-791121bd513899b7dfc0View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , positivesplash10-014i-0090000000-eb3996846ea4f036cccaView in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , positivesplash10-014i-0390000000-a57ce4cfb24ba743c54bView in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , positivesplash10-0006-0950000000-303d99867511fe3a013bView in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , positivesplash10-0006-0930000000-77e720374927be5113efView in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , positivesplash10-0006-0920000000-4a93d8e76eb7d0d59481View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , positivesplash10-03du-0910000000-8ad9f37884e8686ef7baView in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , positivesplash10-03dr-2900000000-2274a3adb5e486f57001View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , positivesplash10-03dr-6900000000-74d56231c43250bc65caView in MoNA LC-MS/MS

    LC-MS/MS Spectrum – , positivesplash10-014i-0490000000-7868daa9f0ec9ebda34aView in MoNA Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 10V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 20V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 40V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 10V, NegativeNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 20V, NegativeNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 40V, NegativeNot Available

    Biological Properties Cellliar Locations

  • Membrane

    • Biofluid Locations

  • Blood
  • Urine

    • Tissue Location

    Not Available Pathways

    Not Available Normal Concentrations

    Biofluid Status Value Age Sex Condition Reference Details BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01006

  • 21059682

    • details UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01006

  • 21059682

    • details

    Abnormal Concentrations

    Not Available Predicted Concentrations

    Biofluid Value Original age Original sex Original condition Comments Blood0-4 uMAdlit (>18 years old)BothNormalPredicted based on drug qualities Blood0-2 umol/mmol creatinineAdlit (>18 years old)BothNormalPredicted based on drug qualities

    Associated Disorders and Diseases Disease References

    None Associated OMIM IDs

    None External Links DrugBank ID

    DB01006 DrugBank Metabolite ID

    Not Available Phenol Explorer Compound ID

    Not Available Phenol Explorer Metabolite ID

    Not Available FoodDB ID

    Not Available KNApSAcK ID

    Not Available Chemspider ID

    3765 KEGG Compound ID

    C08163 BioCyc ID

    Not Available BiGG ID

    Not Available Wikipedia Link

    Letrozole NuGOwiki Link

    HMDB15141 Metagene Link

    HMDB15141 METLIN ID

    Not Available PubChem Compound

    3902 PDB ID

    Not Available ChEBI ID

    6413

    Product: iCRT 15

    References Synthesis Reference Not Available Material Safety Data Sheet (MSDS) Not Available General References
    1. Tulandi T, Martin J, Al-Fadhli R, Kabli N, Forman R, Hitkari J, Librach C, Greenblatt E, Casper RF: Congenital malformations among 911 newborns conceived after infertility treatment with letrozole or clomiphene citrate. Fertil Steril. 2006 Jun;85(6):1761-5. Epub 2006 May 2. [PubMed:16650422 ]

    Enzymes

    General function:
    Involved in monooxygenase activity
    Specific function:
    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. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
    Gene Name:
    CYP3A4
    Uniprot ID:
    P08684
    Molecular weight:
    57255.585
    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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
    General function:
    Involved in monooxygenase activity
    Specific function:
    Catalyzes the formation of aromatic C18 estrogens from C19 androgens.
    Gene Name:
    CYP19A1
    Uniprot ID:
    P11511
    Molecular weight:
    57882.48
    References
    1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
    2. Ebert AD, Bartley J, David M, Schweppe KW: [Aromatase inhibitors–theoretical concept and present experiences in the treatment of endometriosis]. Zentralbl Gynakol. 2003 Jul-Aug;125(7-8):247-51. [PubMed:14505258 ]
    3. Long BJ, Jelovac D, Handratta V, Thiantanawat A, MacPherson N, Ragaz J, Goloubeva OG, Brodie AM: Therapeutic strategies using the aromatase inhibitor letrozole and tamoxifen in a breast cancer model. J Natl Cancer Inst. 2004 Mar 17;96(6):456-65. [PubMed:15026471 ]
    4. Murphy MJ Jr: Molecular Action and Clinical Relevance of Aromatase Inhibitors. Oncologist. 1998;3(2):129-130. [PubMed:10388095 ]
    5. 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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
    General function:
    Involved in monooxygenase activity
    Specific function:
    Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Constitutes the major nicotine C-oxidase. Acts as a 1,4-cineole 2-exo-monooxygenase. Possesses low phenacetin O-deethylation activity.
    Gene Name:
    CYP2A6
    Uniprot ID:
    P11509
    Molecular weight:
    56517.005
    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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]

    PMID: 7666790

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