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Record Information
Version2.0
Creation Date2014-09-11 05:16:24 UTC
Update Date2014-12-24 20:26:57 UTC
Accession NumberT3D4783
Identification
Common NameNilutamide
ClassSmall Molecule
DescriptionNilutamide is an antineoplastic hormonal agent primarily used in the treatment of prostate cancer. Nilutamide is a pure, nonsteroidal anti-androgen with affinity for androgen receptors (but not for progestogen, estrogen, or glucocorticoid receptors). Consequently, Nilutamide blocks the action of androgens of adrenal and testicular origin that stimulate the growth of normal and malignant prostatic tissue. Prostate cancer is mostly androgen-dependent and can be treated with surgical or chemical castration. To date, antiandrogen monotherapy has not consistently been shown to be equivalent to castration.
Compound Type
  • Amide
  • Amine
  • Androgen Antagonist
  • Antineoplastic Agent
  • Drug
  • Metabolite
  • Organic Compound
  • Organofluoride
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
5,5-Dimethyl-3-(alpha,alpha,alpha-trifluoro-4-nitro-m-tolyl)hydantoin
Anandron
Nilandron
Nilutamida
Nilutamidum
Chemical FormulaC12H10F3N3O4
Average Molecular Mass317.221 g/mol
Monoisotopic Mass317.062 g/mol
CAS Registry Number63612-50-0
IUPAC Name5,5-dimethyl-3-[4-nitro-3-(trifluoromethyl)phenyl]imidazolidine-2,4-dione
Traditional Namenilutamide
SMILESCC1(C)N=C(O)N(C1=O)C1=CC(=C(C=C1)N(=O)=O)C(F)(F)F
InChI IdentifierInChI=1S/C12H10F3N3O4/c1-11(2)9(19)17(10(20)16-11)6-3-4-8(18(21)22)7(5-6)12(13,14)15/h3-5H,1-2H3,(H,16,20)
InChI KeyInChIKey=XWXYUMMDTVBTOU-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as phenylhydantoins. These are heterocyclic aromatic compounds containing an imiazolidinedione moiety substituted by a phenyl group.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassAzolidines
Sub ClassImidazolidines
Direct ParentPhenylhydantoins
Alternative Parents
Substituents
  • 3-phenylhydantoin
  • Phenylimidazolidine
  • Alpha-amino acid or derivatives
  • Trifluoromethylbenzene
  • Nitrobenzene
  • Nitroaromatic compound
  • N-acyl urea
  • Ureide
  • Monocyclic benzene moiety
  • Benzenoid
  • Dicarboximide
  • Organic nitro compound
  • C-nitro compound
  • Carbonic acid derivative
  • Urea
  • Azacycle
  • Organic 1,3-dipolar compound
  • Carboxylic acid derivative
  • Propargyl-type 1,3-dipolar organic compound
  • Allyl-type 1,3-dipolar organic compound
  • Organic oxoazanium
  • Carbonyl group
  • Organohalogen compound
  • Organic zwitterion
  • Organic oxygen compound
  • Hydrocarbon derivative
  • Alkyl fluoride
  • Organic nitrogen compound
  • Organofluoride
  • Organonitrogen compound
  • Organooxygen compound
  • Organopnictogen compound
  • Organic oxide
  • Alkyl halide
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • 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 PointNot Available
Boiling PointNot Available
Solubility4.19e-03 g/L
LogP1.8
Predicted Properties
PropertyValueSource
Water Solubility0.0042 g/LALOGPS
logP1.74ALOGPS
logP2.25ChemAxon
logS-4.9ALOGPS
pKa (Strongest Acidic)15.01ChemAxon
pKa (Strongest Basic)-4.4ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area95.23 ŲChemAxon
Rotatable Bond Count3ChemAxon
Refractivity68.23 m³·mol⁻¹ChemAxon
Polarizability25.88 ųChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0a59-9051000000-b212093377487cffc158JSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableJSpectraViewer
LC-MS/MSLC-MS/MS Spectrum - 30V, Negativesplash10-0600-0094000000-0991ece9f9d42b94c643JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 15V, Negativesplash10-014i-0019000000-7989a507a8031f03f612JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 45V, Negativesplash10-00di-0090000000-1d63c70e06fcd4c6d922JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 60V, Negativesplash10-0kmi-0390000000-05fc687a7f642e06e60aJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 60V, Positivesplash10-0kmi-0390000000-e2d42b542bf6dc07d5c0JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 75V, Negativesplash10-0zfr-1970000000-f1091bfdddddc602902cJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 90V, Negativesplash10-0lz9-1920000000-14b04987997234218267JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-014i-0009000000-f4acafe069c7fdcf8fc3JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0a4i-9025000000-2c79c0bbfc87dd118bd7JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0a4l-9000000000-a91f0e83aff94e2bad18JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-014i-0009000000-19746ba07e5113297e15JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-014i-4009000000-f2904499b324cc347c22JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a4l-9000000000-740d06c64bdf821f7e3dJSpectraViewer
Toxicity Profile
Route of ExposureRapidly and completely absorbed, yielding high and persistent plasma concentrations.
Mechanism of ToxicityNilutamide competes with androgen for the binding of androgen receptors, consequently blocking the action of androgens of adrenal and testicular origin that stimulate the growth of normal and malignant prostatic tissue. This blockade of androgen receptors may result in growth arrest or transient tumor regression through inhibition of androgen-dependent DNA and protein synthesis.
MetabolismThe results of a human metabolism study using 14C-radiolabelled tablets show that nilutamide is extensively metabolized and less than 2% of the drug is excreted unchanged in urine after 5 days. Route of Elimination: Nilutamide is extensively metabolized andless than 2% of the drug is excreted unchanged in urine after 5 days. Fecal elimination is negligible, ranging from 1.4% to 7% of the dose after 4 to 5 days. Half Life: 38.0-59.1 hours
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor use in combination with surgical castration for the treatment of metastatic prostate cancer involving distant lymph nodes, bone, or visceral organs (Stage D2).
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsSymptoms of overdose include dizziness, general discomfort, headache, nausea, and vomiting.
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00665
HMDB IDHMDB14803
PubChem Compound ID4493
ChEMBL IDCHEMBL1274
ChemSpider ID4337
KEGG IDC08164
UniProt IDNot Available
OMIM ID
ChEBI ID7573
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkNilutamide
References
Synthesis ReferenceNot Available
MSDSNot Available
General References
  1. Kassouf W, Tanguay S, Aprikian AG: Nilutamide as second line hormone therapy for prostate cancer after androgen ablation fails. J Urol. 2003 May;169(5):1742-4. [12686822 ]
  2. Lukka H, Waldron T, Klotz L, Winquist E, Trachtenberg J: Maximal androgen blockade for the treatment of metastatic prostate cancer--a systematic review. Curr Oncol. 2006 Jun;13(3):81-93. [17576447 ]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Zinc ion 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 and ZIPK/DAPK3.
Gene Name:
AR
Uniprot ID:
P10275
Molecular Weight:
98987.9 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC500.00643 uMNVS_NR_hARNovascreen
AC502.08 uMTox21_AR_BLA_Antagonist_ratioTox21/NCGC
AC504.67 uMTox21_AR_LUC_MDAKB2_AntagonistTox21/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 ]
General Function:
Steroid hydroxylase 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:
55930.545 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC502.26 uMNVS_ADME_hCYP2C19Novascreen
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 ]
General Function:
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
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. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen. Participates in the bioactivation of carcinogenic aromatic and heterocyclic amines. Catalizes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin.
Gene Name:
CYP1A2
Uniprot ID:
P05177
Molecular Weight:
58293.76 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC503.75 uMNVS_ADME_hCYP1A2Novascreen
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 ]
General Function:
Steroid hydroxylase 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. Acts as a 1,4-cineole 2-exo-monooxygenase.
Gene Name:
CYP2B6
Uniprot ID:
P20813
Molecular Weight:
56277.81 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC506.98 uMNVS_ADME_hCYP2B6Novascreen
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 ]