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Identification
Name Nilutamide
Accession Number DB00665 (APRD00150)
Type small molecule
Groups approved
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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Salts Not Available
Brand names
Name Company
Anandron
Nilandron
Nilandrone
Nilutamida [Spanish]
Nilutamide [Usan:Ban:Inn]
Nilutamidum [Latin]
Brand mixtures Not Available
Categories
  • Antineoplastic Agents
  • Androgen Antagonists
CAS number 63612-50-0
Weight Average: 317.2207
Monoisotopic: 317.062340438
Chemical Formula C12H10F3N3O4
InChI Key InChIKey=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)
Plain Text
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
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Nitrobenzenes
Substructures
  • Nitrobenzenes
  • Oxoazaniums
  • Amino Ketones
  • Halogen Derivatives
  • Benzene and Derivatives
  • Ureas and Derivatives
  • Nitro compounds
  • Imidazolidines
  • Heterocyclic compounds
  • Aromatic compounds
  • Carboxamides and Derivatives
  • Carboxylic Acids and Derivatives
  • Anilines
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).
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.
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
Toxicity Symptoms of overdose include dizziness, general discomfort, headache, nausea, and vomiting.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Sanofi aventis us llc
Packagers
Dosage forms
Form Route Strength
Tablet Oral
Prices
Unit description Cost Unit
Nilandron 150 mg tablet 18.03 USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
logP 1.8 Not Available
Predicted Properties
Property Value Source
water solubility 4.19e-03 g/l ALOGPS
logP 1.74 ALOGPS
logP 2.25 ChemAxon
logS -4.9 ALOGPS
pKa (strongest acidic) 15.01 ChemAxon
pKa (strongest basic) -4.4 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 4 ChemAxon
hydrogen donor count 1 ChemAxon
polar surface area 95.23 ChemAxon
rotatable bond count 3 ChemAxon
refractivity 68.23 ChemAxon
polarizability 25.88 ChemAxon
References
Synthesis Reference Not 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
Resource Link
KEGG Drug D00965 Link_out
KEGG Compound C08164 Link_out
PubChem Compound 4493 Link_out
PubChem Substance 46505381 Link_out
ChemSpider 4337 Link_out
ChEBI 7573 Link_out
ChEMBL 7573 Link_out
Therapeutic Targets Database DAP000302 Link_out
PharmGKB PA450632 Link_out
IUPHAR 2864 Link_out
Guide to Pharmacology 2864 Link_out
Drug Product Database 2221861 Link_out
RxList http://www.rxlist.com/cgi/generic2/nilutam.htm Link_out
Drugs.com http://www.drugs.com/cdi/nilutamide.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/nil1294.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Nilutamide Link_out
ATC Codes
  • L02BB02
AHFS Codes
  • 10:00.00
PDB Entries Not Available
FDA label Not Available
MSDS Not Available
Interactions
Drug Interactions
Drug Interaction
Ticlopidine Ticlopidine may decrease the metabolism and clearance of Nilutamide. Consider alternate therapy or monitor for adverse/toxic effects of Nilutamide if Ticlopidine is initiated, discontinued or dose changed.
Food Interactions
  • Avoid alcohol.
  • Take before breakfast.
Targets

1. Androgen receptor

Pharmacological action: yes
Actions: antagonist

The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Activated, but not phosphorylated, by HIPK3

Organism class: human
UniProt ID: P10275 Link_out
Gene: AR Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. NADPH--cytochrome P450 reductase

Actions: substrate

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

UniProt ID: P16435 Link_out
Gene: POR Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

2. Cytochrome P450 2C19

Actions: substrate, inhibitor

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

UniProt ID: P33261 Link_out
Gene: CYP2C19 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

3. Cytochrome P450 2C8

Actions: inhibitor

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. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme responsible for the metabolism the anti- cancer drug paclitaxel (taxol)

UniProt ID: P10632 Link_out
Gene: CYP2C8
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: inhibitor

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

UniProt ID: P11712 Link_out
Gene: CYP2C9
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19