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Record Information
Version4.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:51 UTC
Update Date2017-10-23 19:06:27 UTC
HMDB IDHMDB0015140
Secondary Accession Numbers
  • HMDB15140
Metabolite Identification
Common NameHydroxyurea
DescriptionHydroxyurea is only found in individuals that have used or taken this drug. It is an antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase. [PubChem]Hydroxyurea is converted to a free radical nitroxide (NO) in vivo, and transported by diffusion into cells where it quenches the tyrosyl free radical at the active site of the M2 protein subunit of ribonucleotide reductase, inactivating the enzyme. The entire replicase complex, including ribonucleotide reductase, is inactivated and DNA synthesis is selectively inhibited, producing cell death in S phase and synchronization of the fraction of cells that survive. Repair of DNA damaged by chemicals or irradiation is also inhibited by hydroxyurea, offering potential synergy between hydroxyurea and radiation or alkylating agents. Hydroxyurea also increases the level of fetal hemoglobin, leading to a reduction in the incidence of vasoocclusive crises in sickle cell anemia. Levels of fetal hemoglobin increase in response to activation of soluble guanylyl cyclase (sGC) by hydroxyurea-derived NO.
Structure
Thumb
Synonyms
ValueSource
Carbamohydroxamic acidChEBI
Carbamohydroximic acidChEBI
Carbamoyl oximeChEBI
Carbamyl hydroxamateChEBI
HidroxicarbamidaChEBI
HydreaChEBI
HydroxycarbamidChEBI
HydroxycarbamideChEBI
HydroxycarbamidumChEBI
HydroxyharnstoffChEBI
N-CarbamoylhydroxylamineChEBI
N-HYDROXYUREAChEBI
OxyureaChEBI
CarbamohydroxamateGenerator
CarbamohydroximateGenerator
Carbamyl hydroxamic acidGenerator
Carbamohydroxyamic acidHMDB
HUHMDB
HydroxicarbamidumHMDB
HydroxycarbamineHMDB
HydroxylureaHMDB
IdrossicarbamideHMDB
OncocarbideMeSH
Chemical FormulaCH4N2O2
Average Molecular Weight76.0547
Monoisotopic Molecular Weight76.027277382
IUPAC Namehydroxyurea
Traditional Namehydroxyurea
CAS Registry Number127-07-1
SMILES
NC(=O)NO
InChI Identifier
InChI=1S/CH4N2O2/c2-1(4)3-5/h5H,(H3,2,3,4)
InChI KeyVSNHCAURESNICA-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of chemical entities known as carboximidic acids and derivatives. These are compounds containing a carboximidic group, with the general formula R-C(=NR1)OR2.
KingdomChemical entities
Super ClassOrganic compounds
ClassOrganic acids and derivatives
Sub ClassCarboximidic acids and derivatives
Direct ParentCarboximidic acids and derivatives
Alternative Parents
Substituents
  • Carboximidic acid derivative
  • Organic nitrogen compound
  • Organic oxygen compound
  • Organopnictogen compound
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Imine
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Ontology
Disposition

Biological Location:

  Subcellular:

  Biofluid and excreta:

Route of exposure:

  Enteral:

Role

Industrial application:

  Pharmaceutical industry:

Biological role:

Indirect biological role:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point142 - 146 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility269 g/LNot Available
LogP-1.6Not Available
Predicted Properties
PropertyValueSource
Water Solubility269 g/LALOGPS
logP-1.8ALOGPS
logP-1.4ChemAxon
logS0.55ALOGPS
pKa (Strongest Acidic)10.14ChemAxon
pKa (Strongest Basic)-4.9ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area75.35 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity14.91 m³·mol⁻¹ChemAxon
Polarizability5.94 ųChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
GC-MSGC-MS Spectrum - GC-MS (3 TMS)splash10-0059-3950000000-0418fbb00ea645e9e0ceView in MoNA
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-0059-3950000000-0418fbb00ea645e9e0ceView in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-0002-0920000000-be691e1a11d76d687cc5View in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0006-9000000000-725178d2fb4e3ae0a710View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-03di-9000000000-15e079ef519fdae75dabView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-03di-9000000000-f39d1396b2b03d5846c8View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-01ox-9000000000-b5fb6577ca88b375ebeaView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-0006-9000000000-6093ebde62cb84552dd0View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-004i-9000000000-5f85466dc663205c60f9View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-056r-9000000000-fb233b42b45077d2475dView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-06tf-9000000000-868a329446e04867fc56View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-004i-9000000000-6245f3456e3558782716View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0006-9000000000-722afb6d05d2ca0794f5View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9000000000-f6792fcc64ed7bdb2466View in MoNA
Biological Properties
Cellular Locations
  • Cytoplasm
  • Membrane
Biofluid Locations
  • Blood
  • Urine
Tissue LocationNot Available
PathwaysNot Available
NameSMPDB/PathwhizKEGG
No entries found
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01005 details
UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01005 details
Abnormal Concentrations
Not Available
Predicted Concentrations
BiofluidValueOriginal ageOriginal sexOriginal conditionComments
Blood0-13 uMAdult (>18 years old)BothNormalPredicted based on drug qualities
Blood0-7 umol/mmol creatinineAdult (>18 years old)BothNormalPredicted based on drug qualities
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB01005
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID3530
KEGG Compound IDC07044
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkHydroxyurea
METLIN IDNot Available
PubChem Compound3657
PDB IDNHY
ChEBI ID5816
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Download (PDF)
General ReferencesNot Available

Enzymes

General function:
Involved in oxidation reduction
Specific function:
Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides.
Gene Name:
RRM1
Uniprot ID:
P23921
Molecular weight:
90069.375
References
  1. Culligan K, Tissier A, Britt A: ATR regulates a G2-phase cell-cycle checkpoint in Arabidopsis thaliana. Plant Cell. 2004 May;16(5):1091-104. Epub 2004 Apr 9. [PubMed:15075397 ]
  2. Zhou B, Liu X, Mo X, Xue L, Darwish D, Qiu W, Shih J, Hwu EB, Luh F, Yen Y: The human ribonucleotide reductase subunit hRRM2 complements p53R2 in response to UV-induced DNA repair in cells with mutant p53. Cancer Res. 2003 Oct 15;63(20):6583-94. [PubMed:14583450 ]
  3. Jiang W, Xie J, Varano PT, Krebs C, Bollinger JM Jr: Two distinct mechanisms of inactivation of the class Ic ribonucleotide reductase from Chlamydia trachomatis by hydroxyurea: implications for the protein gating of intersubunit electron transfer. Biochemistry. 2010 Jun 29;49(25):5340-9. doi: 10.1021/bi100037b. [PubMed:20462199 ]
  4. Davies BW, Kohanski MA, Simmons LA, Winkler JA, Collins JJ, Walker GC: Hydroxyurea induces hydroxyl radical-mediated cell death in Escherichia coli. Mol Cell. 2009 Dec 11;36(5):845-60. doi: 10.1016/j.molcel.2009.11.024. [PubMed:20005847 ]
General function:
Involved in monooxygenase activity
Specific function:
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular weight:
55768.94
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]