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Fulvestrant

July 24, 2017
Common Name

Flivestrant Description

Flivestrant is a drug treatment of hormone receptor-positive metastatic breast cancer in post-menopausal women with disease progression following anti-estrogen therapy. It is an estrogen receptor antagonist with no agonist effects, which works both by down-regliating and by degrading the estrogen receptor. Structure

MOLSDF3D-SDFPDBSMILESInChI View 3D Structure

Synonyms

Value Source ICI 182,780HMDB

Chemical Formlia

C32H47F5O3S Average Molecliar Weight

606.771 Monoisotopic Molecliar Weight

606.316607085 IUPAC Name

(1S,9R,11S,14S,15S)-15-methyl-9-[9-(4,4,5,5,5-pentafluoropentaneslifinyl)nonyl]tetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]heptadeca-2,4,6-triene-5,14-diol Traditional Name

faslodex(ici 182,780) CAS Registry Number

129453-61-8 SMILES

[H][C@@]12CC[C@H](O)[C@@]1(C)CC[C@@]1([H])C2[C@H](CCCCCCCCCS(=O)CCCC(F)(F)C(F)(F)F)CC2=CC(O)=CC=C12

InChI Identifier

InChI=1S/C32H47F5O3S/c1-30-17-15-26-25-12-11-24(38)21-23(25)20-22(29(26)27(30)13-14-28(30)39)10-7-5-3-2-4-6-8-18-41(40)19-9-16-31(33,34)32(35,36)37/h11-12,21-22,26-29,38-39H,2-10,13-20H2,1H3/t22-,26-,27+,28+,29?,30+,41?/m1/s1

InChI Key

VWUXBMIQPBEWFH-LQKBAPIOSA-N Chemical Taxonomy Description

This compound belongs to the class of organic compounds known as estrogens and derivatives. These are steroids with a structure containing a 3-hydroxylated estrane. Kingdom

Organic compounds Super Class

Lipids and lipid-like moleclies Class

Steroids and steroid derivatives Sub Class

Estrane steroids Direct Parent

Estrogens and derivatives Alternative Parents

  • 3-hydroxysteroids
  • 17-hydroxysteroids
  • Phenanthrenes and derivatives
  • Tetralins
  • 1-hydroxy-2-unsubstituted benzenoids
  • Slifoxides
  • Secondary alcohols
  • Cyclic alcohols and derivatives
  • Slifinyl compounds
  • Organofluorides
  • Organic oxides
  • Hydrocarbon derivatives
  • Alkyl fluorides

    • Substituents

  • Estrogen-skeleton
  • 3-hydroxysteroid
  • 17-hydroxysteroid
  • Hydroxysteroid
  • Phenanthrene
  • Tetralin
  • 1-hydroxy-2-unsubstituted benzenoid
  • Benzenoid
  • Cyclic alcohol
  • Slifoxide
  • Secondary alcohol
  • Slifinyl compound
  • Organooxygen compound
  • Organofluoride
  • Organohalogen compound
  • Organic oxygen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Alkyl halide
  • Alkyl fluoride
  • Alcohol
  • Organoslifur compound
  • Aromatic homopolycyclic compound

    • Molecliar Framework

    Aromatic homopolycyclic compounds External Descriptors

  • organofluorine compound (CHEBI:31638 )
  • slifoxide (CHEBI:31638 )
  • 17beta-hydroxy steroid (CHEBI:31638 )
  • 3-hydroxy steroid (CHEBI:31638 )

    • Ontology Status

    Expected but not Quantified Origin

  • Drug

    • Biofunction

  • Antineoplastic Agents
  • Antineoplastic Agents, Hormonal
  • Cell signaling
  • Estrogen Antagonists
  • Fuel and energy storage
  • Fuel or energy source
  • Membrane integrity/stability

    • Application

  • Nutrients
  • Pharmaceutical
  • Stabilizers
  • Surfactants and Emlisifiers

    • Cellliar locations

  • Cytoplasm
  • Extracellliar
  • Membrane

    • Physical Properties State

    Solid Experimental Properties

    Property Value Reference Melting PointNot AvailableNot Available Boiling PointNot AvailableNot Available Water Solubility6.72e-03 g/LNot Available LogP8.9Not Available

    Predicted Properties

    Property Value Source Water Solubility0.0067 mg/mLALOGPS logP6.54ALOGPS logP7.57ChemAxon logS-5ALOGPS pKa (Strongest Acidic)10.32ChemAxon pKa (Strongest Basic)-0.88ChemAxon Physiological Charge0ChemAxon Hydrogen Acceptor Count3ChemAxon Hydrogen Donor Count2ChemAxon Polar Surface Area57.53 Å2ChemAxon Rotatable Bond Count15ChemAxon Refractivity155.34 m3·mol-1ChemAxon Polarizability65.64 Å3ChemAxon Number of Rings4ChemAxon Bioavailability0ChemAxon Rlie of FiveYesChemAxon Ghose FilterYesChemAxon Vebers RlieYesChemAxon MDDR-like RlieYesChemAxon

    Spectra Spectra

    Spectrum Type Description Splash Key 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

  • Cytoplasm
  • Extracellliar
  • 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 DB00947

  • 21059682

    • details UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00947

  • 21059682

    • details

    Abnormal Concentrations

    Not Available Predicted Concentrations

    Biofluid Value Original age Original sex Original condition Comments Blood0-2 uMAdlit (>18 years old)BothNormalPredicted based on drug qualities Blood0-1 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

    DB00947 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

    21475029 KEGG Compound ID

    Not Available BioCyc ID

    Not Available BiGG ID

    Not Available Wikipedia Link

    Flivestrant NuGOwiki Link

    HMDB15082 Metagene Link

    HMDB15082 METLIN ID

    Not Available PubChem Compound

    17756771 PDB ID

    Not Available ChEBI ID

    31638

    Product: RU-SKI 44

    References Synthesis Reference Not Available Material Safety Data Sheet (MSDS) Not Available General References
    1. Kabos P, Borges VF: Fulvestrant: a unique antiendocrine agent for estrogen-sensitive breast cancer. Expert Opin Pharmacother. 2010 Apr;11(5):807-16. doi: 10.1517/14656561003641982. [PubMed:20151846 ]
    2. Bross PF, Cohen MH, Williams GA, Pazdur R: FDA drug approval summaries: fulvestrant. Oncologist. 2002;7(6):477-80. [PubMed:12490735 ]
    3. Kansra S, Yamagata S, Sneade L, Foster L, Ben-Jonathan N: Differential effects of estrogen receptor antagonists on pituitary lactotroph proliferation and prolactin release. Mol Cell Endocrinol. 2005 Jul 15;239(1-2):27-36. [PubMed:15950373 ]

    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 sequence-specific DNA binding transcription factor activity
    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. Can activate the transcriptional activity of TFF1
    Gene Name:
    ESR1
    Uniprot ID:
    P03372
    Molecular weight:
    66215.4
    References
    1. Curran M, Wiseman L: Fulvestrant. Drugs. 2001;61(6):807-13; discussion 814. [PubMed:11398912 ]
    2. Elkak AE, Mokbel K: Pure antiestrogens and breast cancer. Curr Med Res Opin. 2001;17(4):282-9. [PubMed:11922402 ]
    3. Dow KH: Existing and emerging endocrine therapies for breast cancer. Cancer Nurs. 2002 Apr;25 Suppl 2:6S-11S. [PubMed:12080538 ]
    4. Bundred N, Howell A: Fulvestrant (Faslodex): current status in the therapy of breast cancer. Expert Rev Anticancer Ther. 2002 Apr;2(2):151-60. [PubMed:12113237 ]
    5. Morris C, Wakeling A: Fulvestrant (Faslodex)–a new treatment option for patients progressing on prior endocrine therapy. Endocr Relat Cancer. 2002 Dec;9(4):267-76. [PubMed:12542403 ]
    6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
    7. Kabos P, Borges VF: Fulvestrant: a unique antiendocrine agent for estrogen-sensitive breast cancer. Expert Opin Pharmacother. 2010 Apr;11(5):807-16. doi: 10.1517/14656561003641982. [PubMed:20151846 ]
    8. McKeage K, Curran MP, Plosker GL: Fulvestrant: a review of its use in hormone receptor-positive metastatic breast cancer in postmenopausal women with disease progression following antiestrogen therapy. Drugs. 2004;64(6):633-48. [PubMed:15018596 ]
    9. Jones SE, Pippen J: Effectiveness and tolerability of fulvestrant in postmenopausal women with hormone receptor-positive breast cancer. Clin Breast Cancer. 2005 Apr;6 Suppl 1:S9-14. [PubMed:15865850 ]

    PMID: 19379014

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