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Bicalutamide

July 24, 2017
Common Name

Bicalutamide Description

Bicalutamide is only found in individuals that have used or taken this drug. It is an oral non-steroidal anti-androgen for prostate cancer. It binds to the androgen receptor.Bicalutamide competes with androgen for the binding of androgen receptors, consequently blocking the action of androgens of adrenal and testicliar origin which stimliate the growth of normal and malignant prostatic tissue. Structure

MOLSDF3D-SDFPDBSMILESInChI View 3D Structure

Synonyms

Value Source CasodexKegg Zeneca brand OF bicalutamideMeSH 4'-cyano-3-(4-Fluorophenylslifonyl)-2-hydroxy-2-methyl-3'-(trifluoromethyl)propionanilideMeSH Astra brand OF bicalutamideMeSH CosudexMeSH AstraZeneca brand OF bicalutamideMeSH

Chemical Formlia

C18H14F4N2O4S Average Molecliar Weight

430.373 Monoisotopic Molecliar Weight

430.061040456 IUPAC Name

N-[4-cyano-3-(trifluoromethyl)phenyl]-3-(4-fluorobenzeneslifonyl)-2-hydroxy-2-methylpropanamide Traditional Name

bicalutamide CAS Registry Number

90357-06-5 SMILES

CC(O)(CS(=O)(=O)C1=CC=C(F)C=C1)C(=O)NC1=CC(=C(C=C1)C#N)C(F)(F)F

InChI Identifier

InChI=1S/C18H14F4N2O4S/c1-17(26,10-29(27,28)14-6-3-12(19)4-7-14)16(25)24-13-5-2-11(9-23)15(8-13)18(20,21)22/h2-8,26H,10H2,1H3,(H,24,25)

InChI Key

LKJPYSCBVHEWIU-UHFFFAOYSA-N Chemical Taxonomy Description

This compound belongs to the class of organic compounds known as trifluoromethylbenzenes. These are organofluorine compounds that contain a benzene ring substituted with one or more trifluoromethyl groups. Kingdom

Organic compounds Super Class

Benzenoids Class

Benzene and substituted derivatives Sub Class

Trifluoromethylbenzenes Direct Parent

Trifluoromethylbenzenes Alternative Parents

  • Anilides
  • Benzeneslifonyl compounds
  • Benzonitriles
  • N-arylamides
  • Fluorobenzenes
  • Aryl fluorides
  • Tertiary alcohols
  • Slifones
  • Secondary carboxylic acid amides
  • Nitriles
  • Organofluorides
  • Organic oxides
  • Hydrocarbon derivatives
  • Carbonyl compounds
  • Alkyl fluorides
  • Organopnictogen compounds

    • Substituents

  • Trifluoromethylbenzene
  • Benzeneslifonyl group
  • Anilide
  • Benzonitrile
  • N-arylamide
  • Fluorobenzene
  • Halobenzene
  • Aryl fluoride
  • Aryl halide
  • Tertiary alcohol
  • Slifonyl
  • Slifone
  • Carboxamide group
  • Secondary carboxylic acid amide
  • Carboxylic acid derivative
  • Carbonitrile
  • Nitrile
  • Organohalogen compound
  • Alkyl halide
  • Organoslifur compound
  • Hydrocarbon derivative
  • Organic oxide
  • Alkyl fluoride
  • Alcohol
  • Carbonyl group
  • Organopnictogen compound
  • Organic oxygen compound
  • Organic nitrogen compound
  • Organofluoride
  • Organonitrogen compound
  • Organooxygen compound
  • Aromatic homomonocyclic compound

    • Molecliar Framework

    Aromatic homomonocyclic compounds External Descriptors

    Not Available Ontology Status

    Expected but not Quantified Origin

  • Drug

    • Biofunction

  • Androgen Antagonists
  • Antineoplastic Agents

    • Application

  • Pharmaceutical

    • Cellliar locations

  • Cytoplasm
  • Membrane

    • Physical Properties State

    Solid Experimental Properties

    Property Value Reference Melting Point191 – 193 °CNot Available Boiling PointNot AvailableNot Available Water Solubility9.28e-03 g/LNot Available LogP2.5Not Available

    Predicted Properties

    Property Value Source Water Solubility0.0093 mg/mLALOGPS logP2.7ALOGPS logP2.71ChemAxon logS-4.7ALOGPS pKa (Strongest Acidic)11.95ChemAxon pKa (Strongest Basic)-4ChemAxon Physiological Charge0ChemAxon Hydrogen Acceptor Count5ChemAxon Hydrogen Donor Count2ChemAxon Polar Surface Area107.26 Å2ChemAxon Rotatable Bond Count6ChemAxon Refractivity96.59 m3·mol-1ChemAxon Polarizability36.68 Å3ChemAxon Number of Rings2ChemAxon 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 – , positivesplash10-014r-2950100000-4088c17274bcf0f095d4View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – , positivesplash10-014r-0980100000-89a3faa58e22068394b8View 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

  • Cytoplasm
  • 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 DB01128

  • 21059682

    • details UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01128

  • 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

    DB01128 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

    2284 KEGG Compound ID

    C08160 BioCyc ID

    Not Available BiGG ID

    Not Available Wikipedia Link

    Bicalutamide NuGOwiki Link

    HMDB15260 Metagene Link

    HMDB15260 METLIN ID

    Not Available PubChem Compound

    2375 PDB ID

    Not Available ChEBI ID

    100717

    Product: X-GAL

    References Synthesis Reference Not Available Material Safety Data Sheet (MSDS) Not Available General References Not Available

    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. Cockshott ID: Bicalutamide: clinical pharmacokinetics and metabolism. Clin Pharmacokinet. 2004;43(13):855-78. [PubMed:15509184 ]
    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 oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan.
    Gene Name:
    CYP2C9
    Uniprot ID:
    P11712
    Molecular weight:
    55627.365
    References
    1. Cockshott ID: Bicalutamide: clinical pharmacokinetics and metabolism. Clin Pharmacokinet. 2004;43(13):855-78. [PubMed:15509184 ]
    General function:
    Involved in monooxygenase activity
    Specific function:
    Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine.
    Gene Name:
    CYP2C19
    Uniprot ID:
    P33261
    Molecular weight:
    55944.565
    References
    1. Cockshott ID: Bicalutamide: clinical pharmacokinetics and metabolism. Clin Pharmacokinet. 2004;43(13):855-78. [PubMed:15509184 ]
    General function:
    Involved in monooxygenase activity
    Specific function:
    Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
    Gene Name:
    CYP2D6
    Uniprot ID:
    P10635
    Molecular weight:
    55768.94
    References
    1. Cockshott ID: Bicalutamide: clinical pharmacokinetics and metabolism. Clin Pharmacokinet. 2004;43(13):855-78. [PubMed:15509184 ]
    General function:
    Involved in DNA binding
    Specific function:
    Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Transcription factor activity is modulated by bound coactivator and corepressor proteins. Transcription activation is down-regulated by NR0B2. Activated, but not phosphorylated, by HIPK3
    Gene Name:
    AR
    Uniprot ID:
    P10275
    Molecular weight:
    98987.9
    References
    1. Wang LG, Liu XM, Kreis W, Budman DR: Androgen antagonistic effect of estramustine phosphate (EMP) metabolites on wild-type and mutated androgen receptor. Biochem Pharmacol. 1998 May 1;55(9):1427-33. [PubMed:10076535 ]
    2. Chang HC, Miyamoto H, Marwah P, Lardy H, Yeh S, Huang KE, Chang C: Suppression of Delta(5)-androstenediol-induced androgen receptor transactivation by selective steroids in human prostate cancer cells. Proc Natl Acad Sci U S A. 1999 Sep 28;96(20):11173-7. [PubMed:10500149 ]
    3. Laufer M, Sinibaldi VJ, Carducci MA, Eisenberger MA: Rapid disease progression after the administration of bicalutamide in patients with metastatic prostate cancer. Urology. 1999 Oct;54(4):745. [PubMed:10754148 ]
    4. Bouchal J, Kolar Z, Madarova J, Hlobilkova A, von Angerer E: The effects of natural ligands of hormone receptors and their antagonists on telomerase activity in the androgen sensitive prostatic cancer cell line LNCaP. Biochem Pharmacol. 2002 Mar 15;63(6):1177-81. [PubMed:11931851 ]
    5. Hara T, Miyazaki J, Araki H, Yamaoka M, Kanzaki N, Kusaka M, Miyamoto M: Novel mutations of androgen receptor: a possible mechanism of bicalutamide withdrawal syndrome. Cancer Res. 2003 Jan 1;63(1):149-53. [PubMed:12517791 ]
    6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]

    PMID: 10942519

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