Tmic
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Record Information
Version2.0
Creation Date2014-09-11 05:15:44 UTC
Update Date2014-12-24 20:26:57 UTC
Accession NumberT3D4767
Identification
Common NameHydroxyurea
ClassSmall Molecule
DescriptionAn antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase.
Compound Type
  • Amine
  • Antineoplastic Agent
  • Antisickling Agent
  • Drug
  • Enzyme Inhibitor
  • Metabolite
  • Nucleic Acid Synthesis Inhibitor
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
Carbamohydroxamic acid
Carbamohydroximic acid
Carbamohydroxyamic acid
Carbamoyl Oxime
Carbamyl Hydroxamate
Droxia
Hidroxicarbamida
HU
Hydrea
Hydroxicarbamidum
Hydroxycarbamid
Hydroxycarbamide
Hydroxycarbamidum
Hydroxycarbamine
Hydroxyharnstoff
Hydroxylurea
Idrossicarbamide
Litalir
N-Carbamoylhydroxylamine
N-Hydroxyurea
Onco-Carbide
Oxyurea
Chemical FormulaCH4N2O2
Average Molecular Mass76.055 g/mol
Monoisotopic Mass76.027 g/mol
CAS Registry Number127-07-1
IUPAC Namehydroxyurea
Traditional Namehydroxyurea
SMILESONC(O)=N
InChI IdentifierInChI=1S/CH4N2O2/c2-1(4)3-5/h5H,(H3,2,3,4)
InChI KeyInChIKey=VSNHCAURESNICA-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as carboximidic acids and derivatives. Carboximidic acids and derivatives are compounds containing a carboximidic group, with the general formula R-C(=NR1)OR2.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboximidic acids and derivatives
Sub ClassNot Available
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
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point133-136°C
Boiling PointNot Available
Solubility1E+006 mg/L (at 25°C)
LogP-1.8
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
Toxicity Profile
Route of ExposureWell absorbed from the gastrointestinal tract.
Mechanism of ToxicityHydroxyurea 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.
MetabolismHepatic. Route of Elimination: Renal excretion is a pathway of elimination. Half Life: 3-4 hours
Toxicity ValuesOral, mouse: LD50 = 7330 mg/kg; Oral, rat: LD50 = 5760 mg/kg
Lethal DoseNot Available
Carcinogenicity (IARC Classification)3, not classifiable as to its carcinogenicity to humans. (1)
Uses/SourcesFor management of melanoma, resistant chronic myelocytic leukemia, and recurrent, metastatic, or inoperable carcinoma of the ovary and Sickle-cell anemia.
Minimum Risk LevelNot Available
Health EffectsTeratogenicity: Teratogenic effects have occurred in experimental animals. Hydroxyurea use during a small number of human pregnancies has been reported. Adverse effects have not been observed in any of the exposed newborns. Reproductive Effects: Adverse reproductive effects have occurred in experimental animals. Mutagenicity: Mutagenic effects have occurred in experimental animals.Mutagenic effects have occurred in humans.
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB01005
HMDB IDHMDB15140
PubChem Compound ID3657
ChEMBL IDCHEMBL467
ChemSpider ID3530
KEGG IDC07044
UniProt IDNot Available
OMIM ID
ChEBI ID5816
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNHY
ACToR IDNot Available
Wikipedia LinkHydroxyurea
References
Synthesis Reference

Dee W. Brooks, Andrew O. Stewart, Richard A. Craig, “Substituted aryl- and heteroarylalkenyl-N-hydroxyurea inhibitors of leukotriene biosynthesis.” U.S. Patent US5506261, issued October, 1990.

MSDSLink
General References
  1. International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor
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 Da
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. [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. [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. [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. [20005847 ]
General Function:
Zinc ion binding
Specific Function:
Nuclear receptor. Interaction with RXR shifts RXR from its role as a silent DNA-binding partner to an active ligand-binding subunit in mediating retinoid responses through target genes defined by LXRES. LXRES are DR4-type response elements characterized by direct repeats of two similar hexanuclotide half-sites spaced by four nucleotides. Plays an important role in the regulation of cholesterol homeostasis, regulating cholesterol uptake through MYLIP-dependent ubiquitination of LDLR, VLDLR and LRP8. Interplays functionally with RORA for the regulation of genes involved in liver metabolism (By similarity). Exhibits a ligand-dependent transcriptional activation activity (PubMed:25661920).
Gene Name:
NR1H3
Uniprot ID:
Q13133
Molecular Weight:
50395.34 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC501.08 uMATG_LXRa_TRANSAttagene
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]