Tmic
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Record Information
Version2.0
Creation Date2014-09-11 05:15:47 UTC
Update Date2014-12-24 20:26:57 UTC
Accession NumberT3D4768
Identification
Common NameFlutamide
ClassSmall Molecule
DescriptionAn antiandrogen with about the same potency as cyproterone in rodent and canine species.
Compound Type
  • Amide
  • Amine
  • Androgen Antagonist
  • Antineoplastic Agent, Hormonal
  • Drug
  • Metabolite
  • Organic Compound
  • Organofluoride
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
4'-Nitro-3'-trifluoromethylisobutyranilide
alpha,alpha,alpha-Trifluoro-2-methyl-4'-nitro-m-propionotoluidide
Andraxan
Antipros
Curestat
Cytomid
Dedile
Drogenil
Elbat
Etaconil
Euflex
Eulexin
Farostat
Flimutal
Flucinom
Flulem
Flutamid
Flutamida
Flutamide USP25
Flutamidum
FTA
NFBA
Niftolid
Niftolide
Odyne
Prostadirex
Prostanon
Chemical FormulaC11H11F3N2O3
Average Molecular Mass276.212 g/mol
Monoisotopic Mass276.072 g/mol
CAS Registry Number13311-84-7
IUPAC Name2-methyl-N-[4-nitro-3-(trifluoromethyl)phenyl]propanamide
Traditional Nameflutamide
SMILESCC(C)C(O)=NC1=CC(=C(C=C1)N(=O)=O)C(F)(F)F
InChI IdentifierInChI=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)
InChI KeyInChIKey=MKXKFYHWDHIYRV-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as trifluoromethylbenzenes. These are organofluorine compounds that contain a benzene ring substituted with one or more trifluoromethyl groups.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassTrifluoromethylbenzenes
Direct ParentTrifluoromethylbenzenes
Alternative Parents
Substituents
  • Trifluoromethylbenzene
  • Nitrobenzene
  • Anilide
  • N-arylamide
  • Nitroaromatic compound
  • Carboxamide group
  • C-nitro compound
  • Organic nitro compound
  • Secondary carboxylic acid amide
  • Carboxylic acid derivative
  • Organic oxoazanium
  • Allyl-type 1,3-dipolar organic compound
  • Propargyl-type 1,3-dipolar organic compound
  • Organic 1,3-dipolar compound
  • Alkyl halide
  • Organooxygen compound
  • Organonitrogen compound
  • Organofluoride
  • Organic oxygen compound
  • Organohalogen compound
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Organopnictogen compound
  • Alkyl fluoride
  • Organic zwitterion
  • Carbonyl group
  • Organic oxide
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point111.5-112.5°C
Boiling PointNot Available
Solubility9.45 mg/L
LogP3.35
Predicted Properties
PropertyValueSource
Water Solubility0.0057 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 Area74.92 ŲChemAxon
Rotatable Bond Count4ChemAxon
Refractivity63.42 m³·mol⁻¹ChemAxon
Polarizability23.2 ųChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0a4l-9280000000-95879ab49ae3474dd134View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-004i-0290000000-cca4c08f2a9bb3fc6f57View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-004i-0190000000-df05faf7e38e6d6da203View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-000i-3900000000-8b7e5888950eed07b29bView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-004i-0090000000-983edf51e9c479db69a5View in MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-004i-0190000000-df05faf7e38e6d6da203View in MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-004i-0290000000-cca4c08f2a9bb3fc6f57View in MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-03di-2940000000-170008eb50a63f0664d0View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-004i-0090000000-7122c7547dc4f518e9faView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00kf-8090000000-02b603738815e91326c2View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-006x-9010000000-19ee080aa7e8861af1ffView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-004i-0090000000-e5a1eaa719d4f63bf6f6View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-004i-2090000000-13768fb84641e8448d75View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0076-9000000000-10b226e4bd1f69316fa1View in MoNA
Toxicity Profile
Route of ExposureRapidly and completely absorbed.
Mechanism of ToxicityFlutamide 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.
MetabolismFlutamide 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.
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the management of locally confined Stage B2-C and Stage D2 metastatic carcinoma of the prostate
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsIn animal studies with flutamide alone, signs of overdose included hypoactivity, piloerection, slow respiration, ataxia, and/or lacrimation, anorexia, tranquilization, emesis, and methemoglobinemia.
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00499
HMDB IDHMDB14642
PubChem Compound ID3397
ChEMBL IDCHEMBL806
ChemSpider ID3280
KEGG IDC07653
UniProt IDNot Available
OMIM ID
ChEBI ID5132
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkFlutamide
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.

MSDSLink
General References
  1. Link [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Transcription regulatory region dna binding
Specific Function:
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. Regulates the circadian clock by inhibiting the basal and circadian expression of the core circadian component PER1. Inhibits PER1 by repressing the CLOCK-ARNTL/BMAL1 heterodimer mediated transcriptional activation of PER1.
Gene Name:
AHR
Uniprot ID:
P35869
Molecular Weight:
96146.705 Da
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. [17327465 ]
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 factor activity is modulated by bound coactivator and corepressor proteins. Transcription activation is down-regulated by NR0B2. Activated, but not phosphorylated, by HIPK3 and ZIPK/DAPK3.
Gene Name:
AR
Uniprot ID:
P10275
Molecular Weight:
98987.9 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC500.342 uMNVS_NR_hARNovascreen
AC507.38 uMTox21_AR_BLA_Antagonist_ratioTox21/NCGC
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Serotonin receptor activity
Specific Function:
This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that stimulate adenylate cyclase. It has a high affinity for tricyclic psychotropic drugs (By similarity). Controls pyramidal neurons migration during corticogenesis, through the regulation of CDK5 activity (By similarity). Is an activator of TOR signaling (PubMed:23027611).
Gene Name:
HTR6
Uniprot ID:
P50406
Molecular Weight:
46953.625 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC502.96 uMNVS_GPCR_h5HT6Novascreen
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
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 imipramine.
Gene Name:
CYP2C19
Uniprot ID:
P33261
Molecular Weight:
55930.545 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC503.15 uMNVS_ADME_hCYP2C19Novascreen
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function:
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. Participates in the bioactivation of carcinogenic aromatic and heterocyclic amines. Catalizes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin.
Gene Name:
CYP1A2
Uniprot ID:
P05177
Molecular Weight:
58293.76 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC504.28 uMNVS_ADME_hCYP1A2Novascreen
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Thromboxane a2 receptor activity
Specific Function:
Receptor for thromboxane A2 (TXA2), a potent stimulator of platelet aggregation. The activity of this receptor is mediated by a G-protein that activates a phosphatidylinositol-calcium second messenger system. In the kidney, the binding of TXA2 to glomerular TP receptors causes intense vasoconstriction. Activates phospholipase C. Isoform 1 activates adenylyl cyclase. Isoform 2 inhibits adenylyl cyclase.
Gene Name:
TBXA2R
Uniprot ID:
P21731
Molecular Weight:
37430.69 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC504.96 uMNVS_GPCR_hTXA2Novascreen
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Zinc ion binding
Specific Function:
Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism and secretion of potentially harmful xenobiotics, drugs and endogenous compounds. Activated by the antibiotic rifampicin and various plant metabolites, such as hyperforin, guggulipid, colupulone, and isoflavones. Response to specific ligands is species-specific. Activated by naturally occurring steroids, such as pregnenolone and progesterone. Binds to a response element in the promoters of the CYP3A4 and ABCB1/MDR1 genes.
Gene Name:
NR1I2
Uniprot ID:
O75469
Molecular Weight:
49761.245 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC507.81 uMATG_PXRE_CISAttagene
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]