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Exemestane

July 24, 2017
Common Name

Exemestane Description

Exemestane is an oral steroidal aromatase inhibitor used in the adjuvant treatment of hormonally-responsive (also called hormone-receptor-positive, estrogen-responsive) breast cancer in postmenopausal women. It acts as a false substrate for the aromatase enzyme, and is processed to an intermediate that binds irreversibly to the active site of the enzyme causing its inactivation. Structure

MOLSDF3D-SDFPDBSMILESInChI View 3D Structure

Synonyms

Value Source 6-Methyleneandrosta-1,4-diene-3,17-dioneChEBI ExemestanoChEBI ExemestanumChEBI ExamestaneMeSH AromasineMeSH AromasilMeSH AromasinMeSH

Chemical Formlia

C20H24O2 Average Molecliar Weight

296.4034 Monoisotopic Molecliar Weight

296.177630012 IUPAC Name

(1S,2R,10R,11S,15S)-2,15-dimethyl-8-methylidenetetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]heptadeca-3,6-diene-5,14-dione Traditional Name

exemestane CAS Registry Number

107868-30-4 SMILES

[H][C@@]12CCC(=O)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CC(=C)C2=CC(=O)C=C[C@]12C

InChI Identifier

InChI=1S/C20H24O2/c1-12-10-14-15-4-5-18(22)20(15,3)9-7-16(14)19(2)8-6-13(21)11-17(12)19/h6,8,11,14-16H,1,4-5,7,9-10H2,2-3H3/t14-,15-,16-,19+,20-/m0/s1

InChI Key

BFYIZQONLCFLEV-DAELLWKTSA-N Chemical Taxonomy Description

This compound belongs to the class of organic compounds known as androgens and derivatives. These are 3-hydroxylated C19 steroid hormones. They are known to favor the development of mascliine characteristics. They also show profound effects on scalp and body hair in humans. Kingdom

Organic compounds Super Class

Lipids and lipid-like moleclies Class

Steroids and steroid derivatives Sub Class

Androstane steroids Direct Parent

Androgens and derivatives Alternative Parents

  • 3-oxo delta-1,4-steroids
  • 17-oxosteroids
  • Delta-1,4-steroids
  • Cyclic ketones
  • Organic oxides
  • Hydrocarbon derivatives

    • Substituents

  • Androgen-skeleton
  • Oxosteroid
  • 17-oxosteroid
  • 3-oxosteroid
  • 3-oxo-delta-1,4-steroid
  • Delta-1,4-steroid
  • Cyclic ketone
  • Ketone
  • Organic oxygen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Organooxygen compound
  • Carbonyl group
  • Aliphatic homopolycyclic compound

    • Molecliar Framework

    Aliphatic homopolycyclic compounds External Descriptors

  • 17-oxo steroid (CHEBI:4953 )
  • 3-oxo-Delta(1),Delta(4)-steroid (CHEBI:4953 )

    • Ontology Status

    Expected but not Quantified Origin

  • Drug

    • Biofunction

  • Antineoplastic Agents
  • Aromatase Inhibitors
  • Cell signaling
  • Fuel and energy storage
  • Fuel or energy source
  • Membrane integrity/stability

    • Application

  • Nutrients
  • Pharmaceutical
  • Stabilizers
  • Surfactants and Emlisifiers

    • Cellliar locations

  • Extracellliar
  • Membrane

    • Physical Properties State

    Solid Experimental Properties

    Property Value Reference Melting Point155.13 °CNot Available Boiling PointNot AvailableNot Available Water Solubility6.83e-03 g/LNot Available LogP3.7Not Available

    Predicted Properties

    Property Value Source Water Solubility0.0068 mg/mLALOGPS logP2.67ALOGPS logP3.87ChemAxon logS-4.6ALOGPS pKa (Strongest Acidic)19.96ChemAxon pKa (Strongest Basic)-5ChemAxon Physiological Charge0ChemAxon Hydrogen Acceptor Count2ChemAxon Hydrogen Donor Count0ChemAxon Polar Surface Area34.14 Å2ChemAxon Rotatable Bond Count0ChemAxon Refractivity89.03 m3·mol-1ChemAxon Polarizability33.71 Å3ChemAxon Number of Rings4ChemAxon 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-QTOF , positivesplash10-0002-0190000000-5e04b3359ea2370bbde1View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QTOF , positivesplash10-0002-0950000000-0daf2c711395130c78a2View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QTOF , positivesplash10-006t-0910000000-58ddee06caa2cdb4eeacView in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QTOF , positivesplash10-006t-0910000000-64dd2bfc1eef30f5b766View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QTOF , positivesplash10-00wa-0900000000-ec533e47176e668d1ee9View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-ITFT , positivesplash10-004i-0980000000-457e7fb9bd5073d9521aView in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-ITFT , positivesplash10-0002-0090000000-cc584f39a06f24401467View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-ITFT , positivesplash10-0002-1960000000-22b6bd7c2ccea9c0c648View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-ITFT , positivesplash10-00dj-2910000000-32edf95f8027c36c74ceView in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-ITFT , positivesplash10-05fu-3900000000-84dacb108ccc2572ab41View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-ITFT , positivesplash10-0596-5900000000-f4ef5b1c0c3093d9be81View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-ITFT , positivesplash10-054o-7900000000-d4fd55a1386141770febView in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-ITFT , positivesplash10-0002-0090000000-d372ca664e7a339d245eView in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-ITFT , positivesplash10-0002-1970000000-6aca0caa93beac3bf271View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-ITFT , positivesplash10-006w-2910000000-2f4bac4fb8744faeb793View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-ITFT , positivesplash10-05fu-3900000000-93e6d94ff92391e3ae17View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-ITFT , positivesplash10-0596-4900000000-3888c20b2af766bfbd28View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-ITFT , positivesplash10-054o-7900000000-e5ae5c87edd46bea9bdfView in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-ITFT , positivesplash10-004i-0890000000-43dff5a59fc535cf2f01View 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

  • 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 DB00990

  • 21059682

    • details UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00990

  • 21059682

    • details

    Abnormal Concentrations

    Not Available Associated Disorders and Diseases Disease References

    None Associated OMIM IDs

    None External Links DrugBank ID

    DB00990 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

    54278 KEGG Compound ID

    C08162 BioCyc ID

    Not Available BiGG ID

    Not Available Wikipedia Link

    Exemestane NuGOwiki Link

    HMDB15125 Metagene Link

    HMDB15125 METLIN ID

    Not Available PubChem Compound

    60198 PDB ID

    EXM ChEBI ID

    4953

    Product: T-5225

    References Synthesis Reference Not Available Material Safety Data Sheet (MSDS) Not Available General References
    1. Robinson A: A review of the use of exemestane in early breast cancer. Ther Clin Risk Manag. 2009 Feb;5(1):91-8. Epub 2009 Mar 26. [PubMed:19436613 ]
    2. Untch M, Jackisch C: Exemestane in early breast cancer: a review. Ther Clin Risk Manag. 2008 Dec;4(6):1295-304. [PubMed:19337436 ]
    3. Abrial C, Durando X, Mouret-Reynier MA, Thivat E, Bayet-Robert M, Nayl B, Dubray P, Pomel C, Chollet P, Penault-Llorca F: Role of neo-adjuvant hormonal therapy in the treatment of breast cancer: a review of clinical trials. Int J Gen Med. 2009 Jul 30;2:129-40. [PubMed:20360896 ]
    4. Nabholtz JM: Long-term safety of aromatase inhibitors in the treatment of breast cancer. Ther Clin Risk Manag. 2008 Feb;4(1):189-204. [PubMed:18728707 ]
    5. Coombes RC, Kilburn LS, Snowdon CF, Paridaens R, Coleman RE, Jones SE, Jassem J, Van de Velde CJ, Delozier T, Alvarez I, Del Mastro L, Ortmann O, Diedrich K, Coates AS, Bajetta E, Holmberg SB, Dodwell D, Mickiewicz E, Andersen J, Lonning PE, Cocconi G, Forbes J, Castiglione M, Stuart N, Stewart A, Fallowfield LJ, Bertelli G, Hall E, Bogle RG, Carpentieri M, Colajori E, Subar M, Ireland E, Bliss JM: Survival and safety of exemestane versus tamoxifen after 2-3 years tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial. Lancet. 2007 Feb 17;369(9561):559-70. [PubMed:17307102 ]

    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. Robinson A: A review of the use of exemestane in early breast cancer. Ther Clin Risk Manag. 2009 Feb;5(1):91-8. Epub 2009 Mar 26. [PubMed:19436613 ]
    2. 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. Koutras A, Giannopoulou E, Kritikou I, Antonacopoulou A, Evans TR, Papavassiliou AG, Kalofonos H: Antiproliferative effect of exemestane in lung cancer cells. Mol Cancer. 2009 Nov 24;8:109. doi: 10.1186/1476-4598-8-109. [PubMed:19930708 ]
    3. Robinson A: A review of the use of exemestane in early breast cancer. Ther Clin Risk Manag. 2009 Feb;5(1):91-8. Epub 2009 Mar 26. [PubMed:19436613 ]
    4. Untch M, Jackisch C: Exemestane in early breast cancer: a review. Ther Clin Risk Manag. 2008 Dec;4(6):1295-304. [PubMed:19337436 ]
    5. Barnadas A, Gil M, Gonzalez S, Tusquets I, Munoz M, Arcusa A, Prieto L, Margeli-Vila M, Moreno A: Exemestane as primary treatment of oestrogen receptor-positive breast cancer in postmenopausal women: a phase II trial. Br J Cancer. 2009 Feb 10;100(3):442-9. doi: 10.1038/sj.bjc.6604868. Epub 2009 Jan 20. [PubMed:19156139 ]
    6. Abrial C, Durando X, Mouret-Reynier MA, Thivat E, Bayet-Robert M, Nayl B, Dubray P, Pomel C, Chollet P, Penault-Llorca F: Role of neo-adjuvant hormonal therapy in the treatment of breast cancer: a review of clinical trials. Int J Gen Med. 2009 Jul 30;2:129-40. [PubMed:20360896 ]
    7. Nabholtz JM: Long-term safety of aromatase inhibitors in the treatment of breast cancer. Ther Clin Risk Manag. 2008 Feb;4(1):189-204. [PubMed:18728707 ]
    8. Brueggemeier RW: Update on the use of aromatase inhibitors in breast cancer. Expert Opin Pharmacother. 2006 Oct;7(14):1919-30. [PubMed:17020418 ]
    9. Brueggemeier RW, Hackett JC, Diaz-Cruz ES: Aromatase inhibitors in the treatment of breast cancer. Endocr Rev. 2005 May;26(3):331-45. Epub 2005 Apr 6. [PubMed:15814851 ]
    10. 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: 11877384

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