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Showing metabocard for Nitisinone (HMDB0014492)

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IdentificationTaxonomyOntologyPhysical propertiesSpectraBiological propertiesConcentrationsLinksReferencesenzymes (1) Show 1 proteinXML
enzymes (1) Show 1 protein
Record Information
Version4.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:49 UTC
Update Date2020-02-26 21:39:45 UTC
HMDB IDHMDB0014492
Secondary Accession Numbers
  • HMDB14492
Metabolite Identification
Common NameNitisinone
DescriptionNitisinone, also known as orfadin or NTBC CPD, belongs to the class of organic compounds known as benzoylcyclohexane-1,3-diones. These are alkyl-phenylketones where the alkyl group is a cyclohexane 1,3-dione. In patients with HT-1, these catabolic intermediates are converted to the toxic metabolites succinylacetone and succinylacetoacetate, which are responsible for the observed liver and kidney toxicity. Nitisinone is a drug which is used as an adjunct to dietary restriction of tyrosine and phenylalanine in the treatment of hereditary tyrosinemia type 1. Nitisinone is an extremely weak basic (essentially neutral) compound (based on its pKa). It is used in the treatment of hereditary tyrosinemia type 1. Nitisinone is only found in individuals that have used or taken this drug. Nitisinone is a competitive inhibitor of 4-hydroxyphenyl-pyruvate dioxygenase, an enzyme upstream of fumarylacetoacetate hydrolyase (FAH) in the tyrosine catabolic pathway. Nitisinone inhibits catabolism of tyrosine by preventing the catabolic intermediates. It is sold under the brand name Orfadin. 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
Data?1582753185
MOLSDFPDBSMILESInChI
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 CPDHMDB
2-(2-Nitro-4-(trifluoromethyl)benzoyl)cyclohexane-1,3-dioneHMDB
2-(2-Nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedioneHMDB
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
Description belongs to the class of organic compounds known as benzoylcyclohexane-1,3-diones. These are alkyl-phenylketones where the alkyl group is a cyclohexane 1,3-dione.
KingdomOrganic compounds
Super ClassOrganic oxygen compounds
ClassOrganooxygen compounds
Sub ClassCarbonyl 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:

Role

Industrial application:

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
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-01ox-9453000000-6678c582428855d7d395Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-001i-0009000000-974033c16a53de383f50Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-056r-1009000000-0631b4574f9b56f2003cSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0006-9020000000-bab1729386f1cfe2969fSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-004i-0009000000-c91cd9c3e89ef6ab4236Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-004i-1009000000-beddd5d5f9f60a53de90Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-000f-9111000000-48ffa1648811e3b1568cSpectrum
Biological Properties
Cellular Locations
  • Membrane (predicted from logP)
Biospecimen Locations
  • Blood
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00348 details
UrineExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00348 details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00348
Phenol Explorer Compound IDNot Available
FooDB 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
Food Biomarker OntologyNot Available
VMH IDNot Available
MarkerDB ID
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General ReferencesNot Available

Enzymes

Enzyme Details
1. 4-hydroxyphenylpyruvate dioxygenase
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 ]