You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
Identification
NameFlutamide
Accession NumberDB00499  (APRD00984)
Typesmall molecule
Groupsapproved
Description

An antiandrogen with about the same potency as cyproterone in rodent and canine species.

Structure
Thumb
Synonyms
SynonymLanguageCode
4'-Nitro-3'-trifluoromethylisobutyranilideNot AvailableNot Available
alpha,alpha,alpha-Trifluoro-2-methyl-4'-nitro-m-propionotoluidideNot AvailableNot Available
EulexinNot AvailableNot Available
FlutamidGermanINN
FlutamidaSpanishINN
FlutamideFrenchINN
FlutamidumLatinINN
FTANot AvailableIS
NFBANot AvailableIS
NiftolidNot AvailableNot Available
NiftolideNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
AndraxanCSC
AntiprosMedicamerc
CurestatAdvanced Pharmaceutical
CytomidCipla
DedileIvax
DrogenilBayer
ElbatGenepharm
EtaconilNolver
EuflexSchering-Plough
EulexinSchering-Plough
FarostatOrion
FlimutalCryopharma
FlucinomMerck Sharp & Dohme
FlulemTeva
OdyneNippon Kayaku
ProstadirexSanofi-Aventis
ProstanonPharmachemie
Brand mixturesNot Available
Categories
CAS number13311-84-7
WeightAverage: 276.2118
Monoisotopic: 276.072176843
Chemical FormulaC11H11F3N2O3
InChI KeyMKXKFYHWDHIYRV-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)
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
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassAnilides
Direct parentAnilides
Alternative parentsNitrobenzenes; Nitro Compounds; Secondary Carboxylic Acid Amides; Nitronic Acids; Organic Oxoazanium Compounds; Carboxylic Acids; Enolates; Polyamines; Organofluorides; Alkyl Fluorides
Substituentsnitronic acid; secondary carboxylic acid amide; carboxamide group; nitro compound; polyamine; enolate; carboxylic acid derivative; carboxylic acid; organic oxoazanium; organofluoride; organohalogen; amine; organonitrogen compound; alkyl halide; alkyl fluoride
Classification descriptionThis compound belongs to the anilides. These are organic heterocyclic compounds derived from oxoacids RkE(=O)l(OH)m (l not 0) by replacing an OH group by the NHPh group or derivative formed by ring substitution.
Pharmacology
IndicationFor the management of locally confined Stage B2-C and Stage D2 metastatic carcinoma of the prostate
PharmacodynamicsFlutamide 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 actionFlutamide 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.
AbsorptionRapidly and completely absorbed.
Volume of distributionNot Available
Protein binding94-96%
Metabolism

Flutamide is rapidly and extensively metabolized, with flutamide comprising only 2.5% of plasma radioactivity 1 hour after administration.

SubstrateEnzymesProduct
Flutamide
2-hydroxyflutamideDetails
Route of eliminationFlutamide 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 lifeThe plasma half-life for the alpha-hydroxylated metabolite of flutamide (an active metabolite) is approximately 6 hours.
ClearanceNot Available
ToxicityIn 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
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9948
Blood Brain Barrier + 0.9655
Caco-2 permeable + 0.7533
P-glycoprotein substrate Non-substrate 0.8131
P-glycoprotein inhibitor I Non-inhibitor 0.8254
P-glycoprotein inhibitor II Non-inhibitor 0.9428
Renal organic cation transporter Non-inhibitor 0.9535
CYP450 2C9 substrate Non-substrate 0.7927
CYP450 2D6 substrate Non-substrate 0.8935
CYP450 3A4 substrate Substrate 0.568
CYP450 1A2 substrate Inhibitor 0.9108
CYP450 2C9 substrate Non-inhibitor 0.6306
CYP450 2D6 substrate Non-inhibitor 0.9231
CYP450 2C19 substrate Inhibitor 0.8994
CYP450 3A4 substrate Non-inhibitor 0.5924
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.6574
Ames test Non AMES toxic 0.5728
Carcinogenicity Carcinogens 0.6077
Biodegradation Not ready biodegradable 0.9924
Rat acute toxicity 2.5770 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9881
hERG inhibition (predictor II) Non-inhibitor 0.8734
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
FormRouteStrength
TabletOral
Prices
Unit descriptionCostUnit
Flutamide 125 mg capsule2.12USDcapsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point111.5-112.5Gold, E.H.; U.S. Patent 3,847,988; November 12, 1974; assigned to Schering Corp.
water solubility9.45 mg/LNot Available
logP3.35MORRIS,JJ ET AL. (1991)
Predicted Properties
PropertyValueSource
water solubility5.66e-03 g/lALOGPS
logP2.55ALOGPS
logP3.27ChemAxon
logS-4.7ALOGPS
pKa (strongest acidic)13.17ChemAxon
pKa (strongest basic)-3.7ChemAxon
physiological charge0ChemAxon
hydrogen acceptor count3ChemAxon
hydrogen donor count1ChemAxon
polar surface area74.92ChemAxon
rotatable bond count4ChemAxon
refractivity63.42ChemAxon
polarizability23.2ChemAxon
number of rings1ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Jack Lawrence James, Louis Frank Molnar, Jr., Tania E. Toney-Parker, “Processes for preparing flutamide compounds and compounds prepared by such processes.” U.S. Patent US 6,228,401, issued November, 1976.

US6228401
General Reference
  1. Link
External Links
ResourceLink
KEGG DrugD00586
KEGG CompoundC07653
PubChem Compound3397
PubChem Substance46508874
ChemSpider3280
ChEBI5132
ChEMBLCHEMBL806
Therapeutic Targets DatabaseDAP000301
PharmGKBPA449685
HETHFT
Drug Product Database2239388
RxListhttp://www.rxlist.com/cgi/generic2/flutam.htm
Drugs.comhttp://www.drugs.com/cdi/flutamide.html
PDRhealthhttp://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/eul1168.shtml
WikipediaFlutamide
ATC CodesL02BB01
AHFS Codes
  • 10:00.00
PDB EntriesNot Available
FDA labelshow(413 KB)
MSDSshow(55.8 KB)
Interactions
Drug Interactions
Drug
TelithromycinTelithromycin 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.
ThiabendazoleThe 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.
VoriconazoleVoriconazole, 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

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Androgen receptor P10275 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: agonist

Components

Name UniProt ID Details
Aryl hydrocarbon receptor P35869 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 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

2. Cytochrome P450 1A2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 1A2 P05177 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 1A1 P04798 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 1B1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 1B1 Q16678 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

5. Cytochrome P450 2C19

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2C19 P33261 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

6. Cytochrome P450 3A5

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A5 P20815 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

Comments
comments powered by Disqus
Drug created on June 13, 2005 07:24 / Updated on April 23, 2014 18:39