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Record Information
Version4.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:49 UTC
Update Date2017-10-23 19:06:18 UTC
HMDB IDHMDB0014492
Secondary Accession Numbers
  • HMDB14492
Metabolite Identification
Common NameNitisinone
DescriptionNitisinone is only found in individuals that have used or taken this drug. It is a synthetic reversible inhibitor of 4-hydroxyphenylpyruvate dioxygenase. It is used in the treatment of hereditary tyrosinemia type 1. It is sold under the brand name Orfadin. [Wikipedia]Nitisinone is a competitive inhibitor of 4-hydroxyphenyl-pyruvate dioxygenase, an enzyme upstream of fumarylacetoacetate hydrolyase (FAH) in the tyrosine catabolic pathway. By inhibiting the normal catabolism of tyrosine in patients with hereditary tyrosinemia type 1 (HT-1), nitisinone prevents the accumulation of the catabolic intermediates maleylacetoacetate and fumarylacetoacetate.
Structure
Thumb
Synonyms
ValueSource
2-(alpha,alpha,alpha-trifluoro-2-nitro-P-Tuluoyl)-1,3-cyclohexanedioneChEBI
NitisinonaChEBI
NitisinonumChEBI
OrfadinChEBI
2-(a,a,a-trifluoro-2-nitro-P-Tuluoyl)-1,3-cyclohexanedioneGenerator
2-(α,α,α-trifluoro-2-nitro-P-tuluoyl)-1,3-cyclohexanedioneGenerator
NTBC CPDMeSH
2-(2-nitro-4-(Trifluoromethyl)benzoyl)cyclohexane-1,3-dioneMeSH
2-(2-nitro-4-Trifluoromethylbenzoyl)-1,3-cyclohexanedioneMeSH
Chemical FormulaC14H10F3NO5
Average Molecular Weight329.2281
Monoisotopic Molecular Weight329.05110705
IUPAC Name2-[2-nitro-4-(trifluoromethyl)benzoyl]cyclohexane-1,3-dione
Traditional Namenitisinone
CAS Registry Number104206-65-7
SMILES
[O-][N+](=O)C1=C(C=CC(=C1)C(F)(F)F)C(=O)C1C(=O)CCCC1=O
InChI Identifier
InChI=1S/C14H10F3NO5/c15-14(16,17)7-4-5-8(9(6-7)18(22)23)13(21)12-10(19)2-1-3-11(12)20/h4-6,12H,1-3H2
InChI KeyOUBCNLGXQFSTLU-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of chemical entities known as benzoylcyclohexane-1,3-diones. These are alkyl-phenylketones where the alkyl group is a cyclohexane 1,3-dione.
KingdomChemical entities
Super ClassOrganic compounds
ClassOrganic oxygen compounds
Sub ClassOrganooxygen compounds
Direct ParentBenzoylcyclohexane-1,3-diones
Alternative Parents
Substituents
  • Benzoylcyclohexane-1,3-dione
  • Trifluoromethylbenzene
  • Nitrobenzene
  • Benzoyl
  • Nitroaromatic compound
  • Aryl alkyl ketone
  • 1,3-diketone
  • Monocyclic benzene moiety
  • 1,3-dicarbonyl compound
  • Benzenoid
  • Organic nitro compound
  • C-nitro compound
  • Cyclic ketone
  • Organic 1,3-dipolar compound
  • Propargyl-type 1,3-dipolar organic compound
  • Organic oxoazanium
  • Allyl-type 1,3-dipolar organic compound
  • Organofluoride
  • Organic oxide
  • Organohalogen compound
  • Organopnictogen compound
  • Hydrocarbon derivative
  • Organic nitrogen compound
  • Organonitrogen compound
  • Alkyl halide
  • Alkyl fluoride
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Ontology
Disposition

Biological Location:

  Subcellular:

  Biofluid and excreta:

Role

Industrial application:

  Pharmaceutical industry:

Biological role:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.0081 g/LNot Available
LogP1.6Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0081 g/LALOGPS
logP2.06ALOGPS
logP3.13ChemAxon
logS-4.6ALOGPS
pKa (Strongest Acidic)2.71ChemAxon
pKa (Strongest Basic)-7.3ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area97.03 ŲChemAxon
Rotatable Bond Count4ChemAxon
Refractivity72.35 m³·mol⁻¹ChemAxon
Polarizability26.74 ųChemAxon
Number of Rings2ChemAxon
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, Positivesplash10-01ox-9453000000-6678c582428855d7d395View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-001i-0009000000-974033c16a53de383f50View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-056r-1009000000-0631b4574f9b56f2003cView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0006-9020000000-bab1729386f1cfe2969fView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-004i-0009000000-c91cd9c3e89ef6ab4236View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-004i-1009000000-beddd5d5f9f60a53de90View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-000f-9111000000-48ffa1648811e3b1568cView in MoNA
Biological Properties
Cellular Locations
  • Membrane (predicted from logP)
Biofluid Locations
  • Blood
  • Urine
Tissue LocationNot Available
PathwaysNot Available
NameSMPDB/PathwhizKEGG
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00348 details
UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00348 details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00348
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID103195
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkNitisinone
METLIN IDNot Available
PubChem Compound115355
PDB IDNot Available
ChEBI ID50378
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General ReferencesNot Available

Enzymes

General function:
Involved in 4-hydroxyphenylpyruvate dioxygenase activity
Specific function:
Key enzyme in the degradation of tyrosine.
Gene Name:
HPD
Uniprot ID:
P32754
Molecular weight:
40497.105
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  2. Fisher AA, Davis MW: Alkaptonuric ochronosis with aortic valve and joint replacements and femoral fracture: a case report and literature review. Clin Med Res. 2004 Nov;2(4):209-15. [PubMed:15931360 ]
  3. Yang DY: 4-Hydroxyphenylpyruvate dioxygenase as a drug discovery target. Drug News Perspect. 2003 Oct;16(8):493-6. [PubMed:14668946 ]
  4. Hanauske-Abel HM, Popowicz A, Remotti H, Newfield RS, Levy J: Tyrosinemia I, a model for human diseases mediated by 2-oxoacid-utilizing dioxygenases: hepatotoxin suppression by NTBC does not normalize hepatic collagen metabolism. J Pediatr Gastroenterol Nutr. 2002 Jul;35(1):73-8. [PubMed:12142814 ]
  5. Suwannarat P, O'Brien K, Perry MB, Sebring N, Bernardini I, Kaiser-Kupfer MI, Rubin BI, Tsilou E, Gerber LH, Gahl WA: Use of nitisinone in patients with alkaptonuria. Metabolism. 2005 Jun;54(6):719-28. [PubMed:15931605 ]
  6. Santra S, Baumann U: Experience of nitisinone for the pharmacological treatment of hereditary tyrosinaemia type 1. Expert Opin Pharmacother. 2008 May;9(7):1229-36. doi: 10.1517/14656566.9.7.1229. [PubMed:18422479 ]