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Identification
NameNilutamide
Accession NumberDB00665  (APRD00150)
TypeSmall Molecule
GroupsApproved
Description

Nilutamide 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.

Structure
Thumb
Synonyms
SynonymLanguageCode
5,5-Dimethyl-3-(alpha,alpha,alpha-trifluoro-4-nitro-m-tolyl)hydantoinNot AvailableNot Available
NilandronNot AvailableNot Available
NilutamidaSpanishNot Available
NilutamideNot AvailableINN, BAN, USAN
NilutamidumLatinNot Available
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Nilandrontablet150 mgoralSanofi Aventis U.S. Llc1996-09-19Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Nilandrontablet150 mgoralCovis Pharmaceuticals, Inc.2013-07-15Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Anandrontablet50 mgoralSanofi Aventis Canada IncNot AvailableNot AvailableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
CAS number63612-50-0
WeightAverage: 317.2207
Monoisotopic: 317.062340438
Chemical FormulaC12H10F3N3O4
InChI KeyXWXYUMMDTVBTOU-UHFFFAOYSA-N
InChI
InChI=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)
IUPAC Name
5,5-dimethyl-3-[4-nitro-3-(trifluoromethyl)phenyl]imidazolidine-2,4-dione
SMILES
CC1(C)NC(=O)N(C1=O)C1=CC(=C(C=C1)[N+]([O-])=O)C(F)(F)F
Taxonomy
DescriptionThis compound 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
  • Nitrobenzene
  • Ureide
  • Benzenoid
  • Monocyclic benzene moiety
  • Organic nitro compound
  • Urea
  • Tertiary amine
  • Organic nitrite
  • C-nitro compound
  • Carboxamide group
  • Azacycle
  • Organic 1,3-dipolar compound
  • Propargyl-type 1,3-dipolar organic compound
  • Allyl-type 1,3-dipolar organic compound
  • Organic oxoazanium
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organic salt
  • Organooxygen compound
  • Organonitrogen compound
  • Organofluoride
  • Organohalogen compound
  • Carbonyl group
  • Amine
  • Alkyl halide
  • Alkyl fluoride
  • Organic zwitterion
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Pharmacology
IndicationFor use in combination with surgical castration for the treatment of metastatic prostate cancer involving distant lymph nodes, bone, or visceral organs (Stage D2).
PharmacodynamicsNilutamide 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. The relative binding affinity of nilutamide at the androgen receptor is less than that of bicalutamide, but similar to that of hydroxuflutamide.
Mechanism of actionNilutamide 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.
AbsorptionRapidly and completely absorbed, yielding high and persistent plasma concentrations.
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

The 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 eliminationNilutamide 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 life38.0-59.1 hours
ClearanceNot Available
ToxicitySymptoms of overdose include dizziness, general discomfort, headache, nausea, and vomiting.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.8491
Caco-2 permeable-0.5254
P-glycoprotein substrateNon-substrate0.637
P-glycoprotein inhibitor INon-inhibitor0.8572
P-glycoprotein inhibitor IINon-inhibitor0.9314
Renal organic cation transporterNon-inhibitor0.9567
CYP450 2C9 substrateNon-substrate0.7776
CYP450 2D6 substrateNon-substrate0.8934
CYP450 3A4 substrateNon-substrate0.527
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 substrateNon-inhibitor0.9071
CYP450 2D6 substrateNon-inhibitor0.9231
CYP450 2C19 substrateInhibitor0.8993
CYP450 3A4 substrateInhibitor0.796
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8293
Ames testAMES toxic0.6671
CarcinogenicityNon-carcinogens0.6032
BiodegradationNot ready biodegradable0.9944
Rat acute toxicity3.0768 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9684
hERG inhibition (predictor II)Non-inhibitor0.8734
Pharmacoeconomics
Manufacturers
  • Sanofi aventis us llc
Packagers
Dosage forms
FormRouteStrength
Tabletoral150 mg
Tabletoral50 mg
Prices
Unit descriptionCostUnit
Nilandron 150 mg tablet18.03USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
logP1.8Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00419 mg/mLALOGPS
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 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity68.23 m3·mol-1ChemAxon
Polarizability25.88 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General Reference
  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. Pubmed
  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. Pubmed
External Links
ATC CodesL02BB02
AHFS Codes
  • 10:00.00
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. Androgen receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Androgen receptor P10275 Details

References:

  1. Raynaud JP: Antiandrogens in combination with LH-RH agonists in prostate cancer. Am J Clin Oncol. 1988;11 Suppl 2:S132-47. Pubmed
  2. Moguilewsky M, Bertagna C, Hucher M: Pharmacological and clinical studies of the antiandrogen Anandron. J Steroid Biochem. 1987;27(4-6):871-5. Pubmed
  3. Raynaud JP, Bonne C, Moguilewsky M, Lefebvre FA, Belanger A, Labrie F: The pure antiandrogen RU 23908 (Anandron), a candidate of choice for the combined antihormonal treatment of prostatic cancer: a review. Prostate. 1984;5(3):299-311. Pubmed
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  5. Labrie F: Hormonal therapy of prostate cancer. Prog Brain Res. 2010;182:321-41. Pubmed
  6. Schasfoort EM, Van De Beek C, Newling DW: Safety and efficacy of a non-steroidal anti-androgen, based on results of a post marketing surveillance of nilutamide. Prostate Cancer Prostatic Dis. 2001;4(2):112-117. Pubmed
  7. Kaisary AV, Iversen P, Tyrrell CJ, Carroll K, Morris T: Is there a role for antiandrogen monotherapy in patients with metastatic prostate cancer? Prostate Cancer Prostatic Dis. 2001;4(4):196-203. Pubmed
  8. Kolvenbag GJ, Furr BJ, Blackledge GR: Receptor affinity and potency of non-steroidal antiandrogens: translation of preclinical findings into clinical activity. Prostate Cancer Prostatic Dis. 1998 Dec;1(6):307-314. Pubmed
  9. Brawer MK, Crawford ED, Labrie F, Mendoza-Valdes A, Miller PD, Petrylak DP: Androgen deprivation and other treatments for advanced prostate cancer. Rev Urol. 2001;3 Suppl 2:S59-68. Pubmed

Enzymes

1. Cytochrome P450 2C19

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C19 P33261 Details

References:

  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  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. Epub 2009 Nov 24. Pubmed

2. NADPH--cytochrome P450 reductase

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
NADPH--cytochrome P450 reductase P16435 Details

References:

  1. Berger V, Berson A, Wolf C, Chachaty C, Fau D, Fromenty B, Pessayre D: Generation of free radicals during the reductive metabolism of nilutamide by lung microsomes: possible role in the development of lung lesions in patients treated with this anti-androgen. Biochem Pharmacol. 1992 Feb 4;43(3):654-7. Pubmed

3. Cytochrome P450 2C8

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C8 P10632 Details

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. Epub 2009 Nov 24. Pubmed

4. Cytochrome P450 2C9

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C9 P11712 Details

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. Epub 2009 Nov 24. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:11