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Identification
NameHydroxyurea
Accession NumberDB01005  (APRD00023)
TypeSmall Molecule
GroupsApproved
DescriptionAn antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase. [PubChem]
Structure
Thumb
Synonyms
Carbamohydroxamic Acid
Carbamohydroximic Acid
Carbamoyl Oxime
Carbamyl Hydroxamate
Hidroxicarbamida
Hydrea
Hydroxycarbamid
Hydroxycarbamide
Hydroxycarbamidum
Hydroxyharnstoff
Hydroxyurea
N-Carbamoylhydroxylamine
N-Hydroxyurea
Oxyurea
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
DroxiaCapsule200 mg/1OralE.R. Squibb & Sons, L.L.C.2009-06-01Not applicableUs
DroxiaCapsule300 mg/1OralE.R. Squibb & Sons, L.L.C.2009-06-01Not applicableUs
DroxiaCapsule400 mg/1OralE.R. Squibb & Sons, L.L.C.2009-06-01Not applicableUs
HydreaCapsule500 mg/1OralE.R. Squibb & Sons, L.L.C.2009-06-01Not applicableUs
Hydrea Cap 500mgCapsule500 mgOralBristol Myers Squibb Canada1979-12-31Not applicableCanada
HydroxyureaCapsule500 mgOralSanis Health Inc2010-02-25Not applicableCanada
Mylan-hydroxyureaCapsule500 mgOralMylan Pharmaceuticals Ulc2001-02-22Not applicableCanada
SiklosTablet, film coated1000 mgOralAddmedica2007-06-29Not applicableEu
SiklosTablet, film coated100 mgOralAddmedica2007-06-29Not applicableEu
SiklosTablet, film coated100 mgOralAddmedica2007-06-29Not applicableEu
SiklosTablet, film coated100 mgOralAddmedica2007-06-29Not applicableEu
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-hydroxyureaCapsule500 mgOralApotex Inc2003-10-22Not applicableCanada
HydroxyureaCapsule500 mg/1OralAv Kare, Inc.2013-07-19Not applicableUs
HydroxyureaCapsule500 mg/1OralTeva Pharmaceuticals USA Inc1998-10-19Not applicableUs
HydroxyureaCapsule500 mg/1OralPhysicians Total Care, Inc.2003-04-11Not applicableUs
HydroxyureaCapsule500 mg/1OralPar Pharmaceutical, Inc.1999-02-24Not applicableUs
HydroxyureaCapsule500 mg/1OralGolden State Medical Supply, Inc.1999-02-24Not applicableUs
HydroxyureaCapsule500 mg/1OralAmerican Health Packaging2008-08-12Not applicableUs
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
LitalirBristol-Myers Squibb
Onco-CarbideTeofarma
Brand mixturesNot Available
SaltsNot Available
Categories
UNIIX6Q56QN5QC
CAS number127-07-1
WeightAverage: 76.0547
Monoisotopic: 76.027277382
Chemical FormulaCH4N2O2
InChI KeyVSNHCAURESNICA-UHFFFAOYSA-N
InChI
InChI=1S/CH4N2O2/c2-1(4)3-5/h5H,(H3,2,3,4)
IUPAC Name
hydroxyurea
SMILES
NC(=O)NO
Pharmacology
IndicationFor management of melanoma, resistant chronic myelocytic leukemia, and recurrent, metastatic, or inoperable carcinoma of the ovary and Sickle-cell anemia.
Structured Indications
PharmacodynamicsHydroxyurea has dose-dependent synergistic activity with cisplatin in vitro. In vivo Hydroxyurea showed activity in combination with cisplatin against the LX-1 and CALU-6 human lung xenografts, but minimal activity was seen with the NCI-H460 or NCI-H520 xenografts. Hydroxyurea was synergistic with cisplatin in the Lewis lung murine xenograft. Sequential exposure to Hydroxyurea 4 hours before cisplatin produced the greatest interaction.
Mechanism of actionHydroxyurea 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.
TargetKindPharmacological actionActionsOrganismUniProt ID
Ribonucleoside-diphosphate reductase large subunitProteinyes
inhibitor
HumanP23921 details
Related Articles
AbsorptionWell absorbed from the gastrointestinal tract.
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Hepatic.

Route of eliminationRenal excretion is a pathway of elimination.
Half life3-4 hours
ClearanceNot Available
ToxicityOral, mouse: LD50 = 7330 mg/kg; Oral, rat: LD50 = 5760 mg/kg Teratogenicity: 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.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Interactions
Drug Interactions
DrugInteractionDrug group
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Hydroxyurea.Approved
ALT-110The risk or severity of adverse effects can be increased when Hydroxyurea is combined with ALT-110.Investigational
AnvirzelAnvirzel may decrease the cardiotoxic activities of Hydroxyurea.Investigational
BcgThe therapeutic efficacy of Bcg can be decreased when used in combination with Hydroxyurea.Investigational
BevacizumabBevacizumab may increase the cardiotoxic activities of Hydroxyurea.Approved, Investigational
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Hydroxyurea.Approved
CDX-110The risk or severity of adverse effects can be increased when Hydroxyurea is combined with CDX-110.Investigational
ClozapineThe risk or severity of adverse effects can be increased when Hydroxyurea is combined with Clozapine.Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Hydroxyurea.Approved, Investigational
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Hydroxyurea.Approved
DeslanosideDeslanoside may decrease the cardiotoxic activities of Hydroxyurea.Approved
DidanosineThe risk or severity of adverse effects can be increased when Hydroxyurea is combined with Didanosine.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Hydroxyurea.Approved
DigoxinDigoxin may decrease the cardiotoxic activities of Hydroxyurea.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Hydroxyurea.Approved, Investigational
FesoterodineThe serum concentration of the active metabolites of Fesoterodine can be increased when Fesoterodine is used in combination with Hydroxyurea.Approved
FingolimodHydroxyurea may increase the immunosuppressive activities of Fingolimod.Approved, Investigational
G17DTThe risk or severity of adverse effects can be increased when Hydroxyurea is combined with G17DT.Investigational
GI-5005The risk or severity of adverse effects can be increased when Hydroxyurea is combined with GI-5005.Investigational
INGN 201The risk or severity of adverse effects can be increased when Hydroxyurea is combined with INGN 201.Investigational
INGN 225The risk or severity of adverse effects can be increased when Hydroxyurea is combined with INGN 225.Investigational
LeflunomideThe risk or severity of adverse effects can be increased when Hydroxyurea is combined with Leflunomide.Approved, Investigational
MetamizoleThe risk or severity of adverse effects can be increased when Metamizole is combined with Hydroxyurea.Withdrawn
MetoprololThe serum concentration of Metoprolol can be increased when it is combined with Hydroxyurea.Approved, Investigational
NatalizumabThe risk or severity of adverse effects can be increased when Hydroxyurea is combined with Natalizumab.Approved, Investigational
OuabainOuabain may decrease the cardiotoxic activities of Hydroxyurea.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Hydroxyurea.Approved, Vet Approved
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Hydroxyurea.Approved, Investigational
Rabies vaccineThe risk or severity of adverse effects can be increased when Hydroxyurea is combined with Rabies vaccine.Approved
Rabies vaccineThe therapeutic efficacy of Rabies vaccine can be decreased when used in combination with Hydroxyurea.Approved
RoflumilastRoflumilast may increase the immunosuppressive activities of Hydroxyurea.Approved
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Hydroxyurea.Approved
SRP 299The risk or severity of adverse effects can be increased when Hydroxyurea is combined with SRP 299.Investigational
StavudineThe risk or severity of adverse effects can be increased when Hydroxyurea is combined with Stavudine.Approved, Investigational
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Hydroxyurea.Approved, Investigational
TG4010The risk or severity of adverse effects can be increased when Hydroxyurea is combined with TG4010.Investigational
ThioridazineThe serum concentration of Thioridazine can be increased when it is combined with Hydroxyurea.Approved
TofacitinibHydroxyurea may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Hydroxyurea.Approved, Investigational
Food Interactions
  • Take without regard to meals. Drink liberally.
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.

US5506261
General ReferencesNot Available
External Links
ATC CodesL01XX05
AHFS Codes
  • 10:00.00
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (75.1 KB)
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9154
Blood Brain Barrier+0.9382
Caco-2 permeable-0.7235
P-glycoprotein substrateNon-substrate0.8437
P-glycoprotein inhibitor INon-inhibitor0.9736
P-glycoprotein inhibitor IINon-inhibitor0.9946
Renal organic cation transporterNon-inhibitor0.9697
CYP450 2C9 substrateNon-substrate0.8063
CYP450 2D6 substrateNon-substrate0.8363
CYP450 3A4 substrateNon-substrate0.7784
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9077
CYP450 2D6 inhibitorNon-inhibitor0.927
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.9072
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9778
Ames testAMES toxic0.8685
CarcinogenicityNon-carcinogens0.6129
BiodegradationNot ready biodegradable0.7305
Rat acute toxicity1.1524 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9846
hERG inhibition (predictor II)Non-inhibitor0.9715
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Bristol myers squibb co
  • Barr laboratories inc
  • Duramed pharmaceuticals inc sub barr laboratories inc
  • Par pharmaceutical inc
  • Roxane laboratories inc
  • Hospira inc
Packagers
Dosage forms
FormRouteStrength
CapsuleOral200 mg/1
CapsuleOral300 mg/1
CapsuleOral400 mg/1
CapsuleOral500 mg/1
CapsuleOral500 mg
Tablet, film coatedOral100 mg
Tablet, film coatedOral1000 mg
Prices
Unit descriptionCostUnit
Hydroxyurea powder2.75USD g
Hydrea 500 mg capsule1.49USD capsule
Droxia 400 mg capsule0.97USD capsule
Droxia 300 mg capsule0.94USD capsule
Droxia 200 mg capsule0.91USD capsule
Hydroxyurea 500 mg capsule0.9USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point133-136U.S. Patent 2,705,727.
water solubility1E+006 mg/L (at 25 °C)MERCK INDEX (1996)
logP-1.80HANSCH,C ET AL. (1995)
logS1.12ADME Research, USCD
Predicted Properties
PropertyValueSource
Water Solubility269.0 mg/mLALOGPS
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 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity14.91 m3·mol-1ChemAxon
Polarizability5.94 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
GC-MSGC-MS Spectrum - GC-MS (3 TMS)splash10-0059-3950000000-0418fbb00ea645e9e0ceView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as organooxygen compounds. These are organic compounds containing a bond between a carbon atom and an oxygen atom.
KingdomOrganic compounds
Super ClassOrganooxygen compounds
ClassNot Available
Sub ClassNot Available
Direct ParentOrganooxygen compounds
Alternative Parents
Substituents
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
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. [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 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Steroid hydroxylase 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 Da
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 ]
Comments
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23