Nilutamide

Identification

Summary

Nilutamide is an antineoplastic hormone used to treat prostate cancer.

Brand Names
Anandron, Nilandron
Generic Name
Nilutamide
DrugBank Accession Number
DB00665
Background

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.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Weight
Average: 317.2207
Monoisotopic: 317.062340438
Chemical Formula
C12H10F3N3O4
Synonyms
  • 5,5-Dimethyl-3-(α,α,α-trifluoro-4-nitro-m-tolyl)hydantoin
  • Nilutamida
  • Nilutamide
  • Nilutamidum
External IDs
  • RU 23908
  • RU-23908

Pharmacology

Indication

For use in combination with surgical castration for the treatment of metastatic prostate cancer involving distant lymph nodes, bone, or visceral organs (Stage D2).

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Adjunct therapy in treatment ofMetastatic prostate cancer••••••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

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. The relative binding affinity of nilutamide at the androgen receptor is less than that of bicalutamide, but similar to that of hydroxuflutamide.

Mechanism of action

Nilutamide 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.

TargetActionsOrganism
AAndrogen receptor
antagonist
Humans
Absorption

Rapidly and completely absorbed, yielding high and persistent plasma concentrations.

Volume of distribution

Not Available

Protein binding

Not 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 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

Clearance

Not Available

Adverse Effects
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Toxicity

Symptoms of overdose include dizziness, general discomfort, headache, nausea, and vomiting.

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirNilutamide may decrease the excretion rate of Abacavir which could result in a higher serum level.
AbataceptThe metabolism of Nilutamide can be increased when combined with Abatacept.
AbrocitinibThe metabolism of Abrocitinib can be decreased when combined with Nilutamide.
AceclofenacAceclofenac may decrease the excretion rate of Nilutamide which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Nilutamide which could result in a higher serum level.
Food Interactions
  • Avoid alcohol.
  • Take separate from meals. Take before breakfast.

Products

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
AnandronTablet50 mgOralCheplapharm Arzneimittel Gmbh1997-08-20Not applicableCanada flag
Anandron - Tab 100mgTablet100 mgOralAventis Pharma Ltd.1997-08-202003-07-22Canada flag
Anandron Tab 100mgTablet100 mg / tabOralHoechst Roussel Canada Inc.1992-12-311999-08-11Canada flag
Anandron Tab 100mgTablet100 mg / tabOralRoussel Canada Inc.1992-12-311996-09-09Canada flag
Anandron Tab 50mgTablet50 mg / tabOralHoechst Roussel Canada Inc.1994-12-311999-08-11Canada flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
NilutamideTablet150 mg/1OralPrasco Laboratories2019-11-22Not applicableUS flag
NilutamideTablet150 mg/1OralANI Pharmaceuticals, Inc.2016-07-18Not applicableUS flag
NilutamideTablet150 mg/1OralCENEXI HSC2019-11-22Not applicableUS flag

Categories

ATC Codes
L02BB02 — Nilutamide
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This 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.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Azolidines
Sub Class
Imidazolidines
Direct Parent
Phenylhydantoins
Alternative Parents
Phenylimidazolidines / Trifluoromethylbenzenes / Alpha amino acids and derivatives / Nitrobenzenes / Nitroaromatic compounds / N-acyl ureas / Dicarboximides / Propargyl-type 1,3-dipolar organic compounds / Azacyclic compounds / Organic oxoazanium compounds
show 8 more
Substituents
3-phenylhydantoin / Alkyl fluoride / Alkyl halide / Allyl-type 1,3-dipolar organic compound / Alpha-amino acid or derivatives / Aromatic heteromonocyclic compound / Azacycle / Benzenoid / C-nitro compound / Carbonic acid derivative
show 25 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
C-nitro compound, imidazolidinone, (trifluoromethyl)benzenes (CHEBI:7573)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
51G6I8B902
CAS number
63612-50-0
InChI Key
XWXYUMMDTVBTOU-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

References

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. [Article]
  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. [Article]
Human Metabolome Database
HMDB0014803
KEGG Drug
D00965
KEGG Compound
C08164
PubChem Compound
4493
PubChem Substance
46505381
ChemSpider
4337
BindingDB
50135912
RxNav
31805
ChEBI
7573
ChEMBL
CHEMBL1274
ZINC
ZINC000003874498
Therapeutic Targets Database
DAP000302
PharmGKB
PA450632
Guide to Pharmacology
GtP Drug Page
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Nilutamide
FDA label
Download (70.5 KB)

Clinical Trials

Clinical Trials

Pharmacoeconomics

Manufacturers
  • Sanofi aventis us llc
Packagers
  • Sanofi-Aventis Inc.
Dosage Forms
FormRouteStrength
TabletOral50 mg
TabletOral100 mg
TabletOral100 mg / tab
TabletOral50 mg / tab
TabletOral150 mg/1
Prices
Unit descriptionCostUnit
Nilandron 150 mg tablet18.03USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
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)-4.5Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count4Chemaxon
Hydrogen Donor Count1Chemaxon
Polar Surface Area92.55 Å2Chemaxon
Rotatable Bond Count3Chemaxon
Refractivity67.22 m3·mol-1Chemaxon
Polarizability25.92 Å3Chemaxon
Number of Rings2Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
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 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorInhibitor0.8993
CYP450 3A4 inhibitorInhibitor0.796
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
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-0a59-9051000000-b212093377487cffc158
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-172.9509716
predicted
DarkChem Lite v0.1.0
[M-H]-160.1407586
predicted
DarkChem Lite v0.1.0
[M-H]-166.05482
predicted
DeepCCS 1.0 (2019)
[M+H]+173.8413716
predicted
DarkChem Lite v0.1.0
[M+H]+174.1338343
predicted
DarkChem Lite v0.1.0
[M+H]+169.72453
predicted
DeepCCS 1.0 (2019)
[M+Na]+173.3218716
predicted
DarkChem Lite v0.1.0
[M+Na]+187.4806902
predicted
DarkChem Lite v0.1.0
[M+Na]+178.28984
predicted
DeepCCS 1.0 (2019)

Targets

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insights and accelerate drug research.
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Details
1. Androgen receptor
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
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 ...
Gene Name
AR
Uniprot ID
P10275
Uniprot Name
Androgen receptor
Molecular Weight
98987.9 Da
References
  1. Raynaud JP: Antiandrogens in combination with LH-RH agonists in prostate cancer. Am J Clin Oncol. 1988;11 Suppl 2:S132-47. [Article]
  2. Moguilewsky M, Bertagna C, Hucher M: Pharmacological and clinical studies of the antiandrogen Anandron. J Steroid Biochem. 1987;27(4-6):871-5. [Article]
  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. [Article]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
  5. Labrie F: Hormonal therapy of prostate cancer. Prog Brain Res. 2010;182:321-41. doi: 10.1016/S0079-6123(10)82014-X. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
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 im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Badowski ME, Burton B, Shaeer KM, Dicristofano J: Oral oncolytic and antiretroviral therapy administration: dose adjustments, drug interactions, and other considerations for clinical use. Drugs Context. 2019 Feb 13;8:212550. doi: 10.7573/dic.212550. eCollection 2019. [Article]
  2. Flockhart Table of Drug Interactions [Link]
  3. niLUTAmide - Cancer Care Ontario [Link]
  4. Nilutamide Monograph - BC Cancer [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, nad(p)h as one donor, and incorporation of one atom of oxygen
Specific Function
This enzyme is required for electron transfer from NADP to cytochrome P450 in microsomes. It can also provide electron transfer to heme oxygenase and cytochrome B5.
Gene Name
POR
Uniprot ID
P16435
Uniprot Name
NADPH--cytochrome P450 reductase
Molecular Weight
76689.12 Da
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. [Article]

Drug created at June 13, 2005 13:24 / Updated at March 18, 2024 16:48