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Identification
Name Flutamide
Accession Number DB00499 (APRD00984)
Type small molecule
Groups approved
Description

An antiandrogen with about the same potency as cyproterone in rodent and canine species.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Flutamide USP25
Salts Not Available
Brand names
Name Company
Cebatrol
Eulexin
Niftholide
Niftolide
Brand mixtures Not Available
Categories
  • Antineoplastic Agents, Hormonal
  • Androgen Antagonists
CAS number 13311-84-7
Weight Average: 276.2118
Monoisotopic: 276.072176843
Chemical Formula C11H11F3N2O3
InChI Key InChIKey=MKXKFYHWDHIYRV-UHFFFAOYSA-N
InChI
InChI=1S/C11H11F3N2O3/c1-6(2)10(17)15-7-3-4-9(16(18)19)8(5-7)11(12,13)14/h3-6H,1-2H3,(H,15,17)
Plain Text
IUPAC Name
2-methyl-N-[4-nitro-3-(trifluoromethyl)phenyl]propanamide
SMILES
CC(C)C(=O)NC1=CC(=C(C=C1)[N+]([O-])=O)C(F)(F)F
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Nitrobenzenes
  • Acetanilides
Substructures
  • Nitrobenzenes
  • Oxoazaniums
  • Amino Ketones
  • Halogen Derivatives
  • Benzene and Derivatives
  • Acetanilides
  • Carboxylic Acids and Derivatives
  • Nitro compounds
  • Aromatic compounds
  • Carboxamides and Derivatives
  • Anilines
Pharmacology
Indication For the management of locally confined Stage B2-C and Stage D2 metastatic carcinoma of the prostate
Pharmacodynamics Flutamide is a nonsteroidal antiandrogen. In animal studies, flutamide demonstrates potent antiandrogenic effects. It exerts its antiandrogenic action by inhibiting androgen uptake and/or by inhibiting nuclear binding of androgen in target tissues or both. Prostatic carcinoma is known to be androgen-sensitive and responds to treatment that counteracts the effect of androgen and/or removes the source of androgen, e.g. castration. Elevations of plasma testosterone and estradiol levels have been noted following flutamide administration.
Mechanism of action Flutamide is a nonsteroidal antiandrogen that blocks the action of both endogenous and exogenous testosterone by binding to the androgen receptor. In addition Flutamide is a potent inhibitor of testosterone-stimulated prostatic DNA synthesis. Moreover, it is capable of inhibiting prostatic nuclear uptake of androgen.
Absorption Rapidly and completely absorbed.
Volume of distribution Not Available
Protein binding 94-96%
Metabolism Flutamide is rapidly and extensively metabolized, with flutamide comprising only 2.5% of plasma radioactivity 1 hour after administration.
Route of elimination Flutamide and its metabolites are excreted mainly in the urine with only 4.2% of a single dose excreted in the feces over 72 hours.
Half life The plasma half-life for the alpha-hydroxylated metabolite of flutamide (an active metabolite) is approximately 6 hours.
Clearance Not Available
Toxicity In animal studies with flutamide alone, signs of overdose included hypoactivity, piloerection, slow respiration, ataxia, and/or lacrimation, anorexia, tranquilization, emesis, and methemoglobinemia.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Schering corp sub schering plough corp
  • Genpharm inc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Par pharmaceutical inc
  • Sandoz inc
  • Watson laboratories inc
Packagers
Dosage forms
Form Route Strength
Tablet Oral
Prices
Unit description Cost Unit
Flutamide 125 mg capsule 2.12 USD capsule
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
melting point 111-113 °C Not Available
water solubility 9.45 mg/L Not Available
logP 3.35 MORRIS,JJ ET AL. (1991)
Predicted Properties
Property Value Source
water solubility 5.66e-03 g/l ALOGPS
logP 2.55 ALOGPS
logP 3.27 ChemAxon
logS -4.7 ALOGPS
pKa (strongest acidic) 13.17 ChemAxon
pKa (strongest basic) -3.7 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 3 ChemAxon
hydrogen donor count 1 ChemAxon
polar surface area 74.92 ChemAxon
rotatable bond count 4 ChemAxon
refractivity 63.42 ChemAxon
polarizability 23.2 ChemAxon
References
Synthesis Reference Not Available
General Reference
  1. Link
External Links
Resource Link
KEGG Drug D00586 Link_out
KEGG Compound C07653 Link_out
PubChem Compound 3397 Link_out
PubChem Substance 46508874 Link_out
ChemSpider 3280 Link_out
ChEBI 5132 Link_out
ChEMBL 5132 Link_out
Therapeutic Targets Database DAP000301 Link_out
PharmGKB PA449685 Link_out
HET HFT Link_out
Drug Product Database 2239388 Link_out
RxList http://www.rxlist.com/cgi/generic2/flutam.htm Link_out
Drugs.com http://www.drugs.com/cdi/flutamide.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/eul1168.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Flutamide Link_out
ATC Codes
  • L02BB01
AHFS Codes
  • 10:00.00
PDB Entries Not Available
FDA label show (413 KB)
MSDS show (55.8 KB)
Interactions
Drug Interactions
Drug Interaction
Telithromycin Telithromycin may reduce clearance of Flutamide. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Flutamide if Telithromycin is initiated, discontinued or dose changed.
Thiabendazole The strong CYP1A2 inhibitor, Thiabendazole, may increase the effects and toxicity of Flutamide by decreasing Flutamide metabolism and clearance. Monitor for changes in the therapeutic and adverse effects of Flutamide if Thiabendazole is initiated, discontinued or dose changed.
Voriconazole Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of flutamide by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of flutamide if voriconazole is initiated, discontinued or dose changed.
Food Interactions
  • Take without regard to meals.
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. 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
  2. Martelli A, Campart GB, Carrozzino R, Ghia M, Mattioli F, Mereto E, Orsi P, Puglia CP: Evaluation of flutamide genotoxicity in rats and in primary human hepatocytes. Pharmacol Toxicol. 2000 Mar;86(3):129-34. Pubmed
  3. Montalvo L, Carmena MJ, Solano RM, Clemente C, Roman ID, Sanchez-Chapado M, Prieto JC: Effect of flutamide-induced androgen-receptor blockade on adenylate cyclase activation through G-protein coupled receptors in rat prostate. Cell Signal. 2000 May;12(5):311-6. Pubmed
  4. Pazos F, Sanchez-Franco F, Balsa JA, Escalada J, Palacios N, Cacicedo L: Mechanisms of reduced body growth in the pubertal feminized male rat: unbalanced estrogen and androgen action on the somatotropic axis. Pediatr Res. 2000 Jul;48(1):96-103. Pubmed
  5. Shilling AD, Williams DE: The non-aromatizable androgen, dihydrotestosterone, induces antiestrogenic responses in the rainbow trout. J Steroid Biochem Mol Biol. 2000 Nov 15;74(4):187-94. Pubmed
  6. Balk SP: Androgen receptor as a target in androgen-independent prostate cancer. Urology. 2002 Sep;60(3 Suppl 1):132-8; discussion 138-9. Pubmed
  7. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Aryl hydrocarbon receptor

Pharmacological action: unknown
Actions: agonist

Ligand-activated transcriptional activator. Binds to the XRE promoter region of genes it activates. Activates the expression of multiple phase I and II xenobiotic chemical metabolizing enzyme genes (such as the CYP1A1 gene). Mediates biochemical and toxic effects of halogenated aromatic hydrocarbons. Involved in cell-cycle regulation. Likely to play an important role in the development and maturation of many tissues

Organism class: human
UniProt ID: P35869 Link_out
Gene: AHR Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Hu W, Sorrentino C, Denison MS, Kolaja K, Fielden MR: Induction of cyp1a1 is a nonspecific biomarker of aryl hydrocarbon receptor activation: results of large scale screening of pharmaceuticals and toxicants in vivo and in vitro. Mol Pharmacol. 2007 Jun;71(6):1475-86. Epub 2007 Feb 27. Pubmed
Enzymes

1. Cytochrome P450 3A4

Actions: substrate

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. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
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

2. Cytochrome P450 1A2

Actions: substrate, 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. 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

UniProt ID: P05177 Link_out
Gene: CYP1A2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Wang B, Zhou SF: Synthetic and natural compounds that interact with human cytochrome P450 1A2 and implications in drug development. Curr Med Chem. 2009;16(31):4066-218. Pubmed
  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. Shet MS, McPhaul M, Fisher CW, Stallings NR, Estabrook RW: Metabolism of the antiandrogenic drug (Flutamide) by human CYP1A2. Drug Metab Dispos. 1997 Nov;25(11):1298-303. Pubmed

3. Cytochrome P450 1A1

Actions: substrate

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

UniProt ID: P04798 Link_out
Gene: CYP1A1 Link_out
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 1B1

Actions: substrate, inhibitor

Participates in the metabolism of an as-yet-unknown biologically active molecule that is a participant in eye development

UniProt ID: Q16678 Link_out
Gene: CYP1B1 Link_out
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

5. Cytochrome P450 2C19

Actions: substrate

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. 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

6. Cytochrome P450 3A5

Actions: substrate

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

UniProt ID: P20815 Link_out
Gene: CYP3A5 Link_out
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