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Record Information
Version5.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:49 UTC
Update Date2022-03-07 02:51:38 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
Data?1582753185
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
Physiological effectNot Available
Disposition
ProcessNot Available
RoleNot Available
Physical Properties
StateSolid
Experimental Molecular Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.0081 g/LNot Available
LogP1.6Not Available
Experimental Chromatographic PropertiesNot Available
Predicted Molecular 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
Predicted Chromatographic Properties

Predicted Collision Cross Sections

PredictorAdduct TypeCCS Value (Å2)Reference
DeepCCS[M+H]+169.17130932474
DeepCCS[M-H]-166.81330932474
DeepCCS[M-2H]-200.32830932474
DeepCCS[M+Na]+175.53630932474
AllCCS[M+H]+170.532859911
AllCCS[M+H-H2O]+167.232859911
AllCCS[M+NH4]+173.632859911
AllCCS[M+Na]+174.532859911
AllCCS[M-H]-168.032859911
AllCCS[M+Na-2H]-167.532859911
AllCCS[M+HCOO]-167.132859911

Predicted Kovats Retention Indices

Underivatized

MetaboliteSMILESKovats RI ValueColumn TypeReference
Nitisinone[O-][N+](=O)C1=C(C=CC(=C1)C(F)(F)F)C(=O)C1C(=O)CCCC1=O2283.1Standard polar33892256
Nitisinone[O-][N+](=O)C1=C(C=CC(=C1)C(F)(F)F)C(=O)C1C(=O)CCCC1=O2107.5Standard non polar33892256
Nitisinone[O-][N+](=O)C1=C(C=CC(=C1)C(F)(F)F)C(=O)C1C(=O)CCCC1=O2086.0Semi standard non polar33892256

Derivatized

Derivative Name / StructureSMILESKovats RI ValueColumn TypeReference
Nitisinone,1TMS,isomer #1C[Si](C)(C)OC1=C(C(=O)C2=CC=C(C(F)(F)F)C=C2[N+](=O)[O-])C(=O)CCC12171.5Semi standard non polar33892256
Nitisinone,1TMS,isomer #1C[Si](C)(C)OC1=C(C(=O)C2=CC=C(C(F)(F)F)C=C2[N+](=O)[O-])C(=O)CCC12212.5Standard non polar33892256
Nitisinone,1TMS,isomer #1C[Si](C)(C)OC1=C(C(=O)C2=CC=C(C(F)(F)F)C=C2[N+](=O)[O-])C(=O)CCC12665.1Standard polar33892256
Nitisinone,1TMS,isomer #2C[Si](C)(C)OC1=CCCC(=O)C1C(=O)C1=CC=C(C(F)(F)F)C=C1[N+](=O)[O-]2164.9Semi standard non polar33892256
Nitisinone,1TMS,isomer #2C[Si](C)(C)OC1=CCCC(=O)C1C(=O)C1=CC=C(C(F)(F)F)C=C1[N+](=O)[O-]2231.3Standard non polar33892256
Nitisinone,1TMS,isomer #2C[Si](C)(C)OC1=CCCC(=O)C1C(=O)C1=CC=C(C(F)(F)F)C=C1[N+](=O)[O-]2681.8Standard polar33892256
Nitisinone,2TMS,isomer #1C[Si](C)(C)OC1=CCCC(O[Si](C)(C)C)=C1C(=O)C1=CC=C(C(F)(F)F)C=C1[N+](=O)[O-]2219.0Semi standard non polar33892256
Nitisinone,2TMS,isomer #1C[Si](C)(C)OC1=CCCC(O[Si](C)(C)C)=C1C(=O)C1=CC=C(C(F)(F)F)C=C1[N+](=O)[O-]2361.8Standard non polar33892256
Nitisinone,2TMS,isomer #1C[Si](C)(C)OC1=CCCC(O[Si](C)(C)C)=C1C(=O)C1=CC=C(C(F)(F)F)C=C1[N+](=O)[O-]2584.9Standard polar33892256
Nitisinone,2TMS,isomer #2C[Si](C)(C)OC1=CCC=C(O[Si](C)(C)C)C1C(=O)C1=CC=C(C(F)(F)F)C=C1[N+](=O)[O-]2210.7Semi standard non polar33892256
Nitisinone,2TMS,isomer #2C[Si](C)(C)OC1=CCC=C(O[Si](C)(C)C)C1C(=O)C1=CC=C(C(F)(F)F)C=C1[N+](=O)[O-]2353.5Standard non polar33892256
Nitisinone,2TMS,isomer #2C[Si](C)(C)OC1=CCC=C(O[Si](C)(C)C)C1C(=O)C1=CC=C(C(F)(F)F)C=C1[N+](=O)[O-]2594.2Standard polar33892256
Nitisinone,1TBDMS,isomer #1CC(C)(C)[Si](C)(C)OC1=C(C(=O)C2=CC=C(C(F)(F)F)C=C2[N+](=O)[O-])C(=O)CCC12407.8Semi standard non polar33892256
Nitisinone,1TBDMS,isomer #1CC(C)(C)[Si](C)(C)OC1=C(C(=O)C2=CC=C(C(F)(F)F)C=C2[N+](=O)[O-])C(=O)CCC12421.8Standard non polar33892256
Nitisinone,1TBDMS,isomer #1CC(C)(C)[Si](C)(C)OC1=C(C(=O)C2=CC=C(C(F)(F)F)C=C2[N+](=O)[O-])C(=O)CCC12718.1Standard polar33892256
Nitisinone,1TBDMS,isomer #2CC(C)(C)[Si](C)(C)OC1=CCCC(=O)C1C(=O)C1=CC=C(C(F)(F)F)C=C1[N+](=O)[O-]2391.9Semi standard non polar33892256
Nitisinone,1TBDMS,isomer #2CC(C)(C)[Si](C)(C)OC1=CCCC(=O)C1C(=O)C1=CC=C(C(F)(F)F)C=C1[N+](=O)[O-]2421.5Standard non polar33892256
Nitisinone,1TBDMS,isomer #2CC(C)(C)[Si](C)(C)OC1=CCCC(=O)C1C(=O)C1=CC=C(C(F)(F)F)C=C1[N+](=O)[O-]2722.8Standard polar33892256
Nitisinone,2TBDMS,isomer #1CC(C)(C)[Si](C)(C)OC1=CCCC(O[Si](C)(C)C(C)(C)C)=C1C(=O)C1=CC=C(C(F)(F)F)C=C1[N+](=O)[O-]2692.0Semi standard non polar33892256
Nitisinone,2TBDMS,isomer #1CC(C)(C)[Si](C)(C)OC1=CCCC(O[Si](C)(C)C(C)(C)C)=C1C(=O)C1=CC=C(C(F)(F)F)C=C1[N+](=O)[O-]2702.2Standard non polar33892256
Nitisinone,2TBDMS,isomer #1CC(C)(C)[Si](C)(C)OC1=CCCC(O[Si](C)(C)C(C)(C)C)=C1C(=O)C1=CC=C(C(F)(F)F)C=C1[N+](=O)[O-]2716.6Standard polar33892256
Nitisinone,2TBDMS,isomer #2CC(C)(C)[Si](C)(C)OC1=CCC=C(O[Si](C)(C)C(C)(C)C)C1C(=O)C1=CC=C(C(F)(F)F)C=C1[N+](=O)[O-]2678.0Semi standard non polar33892256
Nitisinone,2TBDMS,isomer #2CC(C)(C)[Si](C)(C)OC1=CCC=C(O[Si](C)(C)C(C)(C)C)C1C(=O)C1=CC=C(C(F)(F)F)C=C1[N+](=O)[O-]2699.8Standard non polar33892256
Nitisinone,2TBDMS,isomer #2CC(C)(C)[Si](C)(C)OC1=CCC=C(O[Si](C)(C)C(C)(C)C)C1C(=O)C1=CC=C(C(F)(F)F)C=C1[N+](=O)[O-]2718.5Standard polar33892256
Spectra

GC-MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Predicted GC-MSPredicted GC-MS Spectrum - Nitisinone GC-MS (Non-derivatized) - 70eV, Positivesplash10-01ox-9453000000-6678c582428855d7d3952017-09-01Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Nitisinone GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12Wishart LabView Spectrum

MS/MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Nitisinone 10V, Positive-QTOFsplash10-001i-0009000000-974033c16a53de383f502016-08-01Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Nitisinone 20V, Positive-QTOFsplash10-056r-1009000000-0631b4574f9b56f2003c2016-08-01Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Nitisinone 40V, Positive-QTOFsplash10-0006-9020000000-bab1729386f1cfe2969f2016-08-01Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Nitisinone 10V, Negative-QTOFsplash10-004i-0009000000-c91cd9c3e89ef6ab42362016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Nitisinone 20V, Negative-QTOFsplash10-004i-1009000000-beddd5d5f9f60a53de902016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Nitisinone 40V, Negative-QTOFsplash10-000f-9111000000-48ffa1648811e3b1568c2016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Nitisinone 10V, Positive-QTOFsplash10-0089-0069000000-d1a96c2d31f1c560e24d2021-09-22Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Nitisinone 20V, Positive-QTOFsplash10-0229-0193000000-7d678116b1886af267192021-09-22Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Nitisinone 40V, Positive-QTOFsplash10-01vo-9870000000-f537fa57d0461d07f35b2021-09-22Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Nitisinone 10V, Negative-QTOFsplash10-004i-0009000000-587b0e6655b2caea942f2021-09-23Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Nitisinone 20V, Negative-QTOFsplash10-004i-0019000000-d789457835a608d224da2021-09-23Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Nitisinone 40V, Negative-QTOFsplash10-0007-9070000000-25cbb0124c94b26c66b72021-09-23Wishart LabView Spectrum
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 IDNot Available
Good Scents IDNot Available
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 ]