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Record Information
Version3.6
Creation Date2012-09-06 15:16:49 UTC
Update Date2016-02-11 01:28:43 UTC
HMDB IDHMDB14492
Secondary Accession NumbersNone
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
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 KeyInChIKey=OUBCNLGXQFSTLU-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as nitrobenzenes. These are compounds containing a nitrobenzene moiety, which consists of a benzene ring with a carbon bearing a nitro group.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassNitrobenzenes
Direct ParentNitrobenzenes
Alternative Parents
Substituents
  • Nitrobenzene
  • Acetophenone
  • Aryl alkyl ketone
  • Aryl ketone
  • Benzoyl
  • 1,3-diketone
  • Cyclohexanone
  • 1,3-dicarbonyl compound
  • Organic nitro compound
  • Cyclic ketone
  • Organic nitrite
  • C-nitro compound
  • Ketone
  • Organic 1,3-dipolar compound
  • Propargyl-type 1,3-dipolar organic compound
  • Allyl-type 1,3-dipolar organic compound
  • Organic oxoazanium
  • Hydrocarbon derivative
  • Organic salt
  • Organooxygen compound
  • Organonitrogen compound
  • Organofluoride
  • Organohalogen compound
  • Carbonyl group
  • Alkyl halide
  • Alkyl fluoride
  • Organic zwitterion
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Ontology
StatusExpected but not Quantified
Origin
  • Drug
Biofunction
  • Enzyme Inhibitors
Application
  • Pharmaceutical
Cellular locations
  • Membrane (predicted from logP)
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water Solubility8.11e-03 g/LNot Available
LogP1.6Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0081 mg/mLALOGPS
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 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity72.35 m3·mol-1ChemAxon
Polarizability26.74 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
SpectraNot Available
Biological Properties
Cellular Locations
  • Membrane (predicted from logP)
Biofluid Locations
  • Blood
  • Urine
Tissue LocationNot Available
PathwaysNot Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00348
  • Not Applicable
details
UrineExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00348
  • Not Applicable
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
NuGOwiki LinkHMDB14492
Metagene LinkHMDB14492
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. [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. [15931360 ]
  3. Yang DY: 4-Hydroxyphenylpyruvate dioxygenase as a drug discovery target. Drug News Perspect. 2003 Oct;16(8):493-6. [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. [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. [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. [18422479 ]