Identification

Name
Hydroxyurea
Accession Number
DB01005
Description

An antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase.

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 76.0547
Monoisotopic: 76.027277382
Chemical Formula
CH4N2O2
Synonyms
  • Carbamohydroxamic acid
  • Carbamohydroximic acid
  • Carbamoyl oxime
  • Carbamyl hydroxamate
  • Hidroxicarbamida
  • Hydrea
  • Hydroxycarbamid
  • Hydroxycarbamide
  • Hydroxycarbamidum
  • Hydroxyharnstoff
  • Hydroxyurea
  • N-Carbamoylhydroxylamine
  • N-Hydroxyurea
  • Oxyurea
External IDs
  • NSC-32065
  • SQ 1089
  • SQ-1089

Pharmacology

Indication

For management of melanoma, resistant chronic myelocytic leukemia, and recurrent, metastatic, or inoperable carcinoma of the ovary and Sickle-cell anemia.

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
Learn More
Pharmacodynamics

Hydroxyurea 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 action

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.

TargetActionsOrganism
ARibonucleoside-diphosphate reductase large subunit
inhibitor
Humans
Absorption

Well absorbed from the gastrointestinal tract.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Hepatic.

Route of elimination

Renal excretion is a pathway of elimination.

Half-life

3-4 hours

Clearance
Not Available
Adverse Effects
Learn about our commercial Adverse Effects data.
Learn More
Toxicity

Oral, 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
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbataceptThe risk or severity of adverse effects can be increased when Hydroxyurea is combined with Abatacept.
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with Hydroxyurea.
AcebutololThe metabolism of Acebutolol can be decreased when combined with Hydroxyurea.
AcenocoumarolThe risk or severity of bleeding can be increased when Acenocoumarol is combined with Hydroxyurea.
AcetaminophenThe metabolism of Acetaminophen can be decreased when combined with Hydroxyurea.
Acetylsalicylic acidThe risk or severity of bleeding can be increased when Acetylsalicylic acid is combined with Hydroxyurea.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Hydroxyurea.
Adenovirus type 7 vaccine liveThe risk or severity of infection can be increased when Adenovirus type 7 vaccine live is combined with Hydroxyurea.
AldesleukinThe risk or severity of adverse effects can be increased when Aldesleukin is combined with Hydroxyurea.
AlefaceptThe risk or severity of adverse effects can be increased when Alefacept is combined with Hydroxyurea.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

    Learn more
  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

    Learn more
  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

    Learn more
  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

    Learn more
Food Interactions
  • Drink plenty of fluids.
  • Take with or without food.

Products

Product Images
International/Other Brands
Litalir (Bristol-Myers Squibb) / Onco-Carbide (Teofarma)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
DroxiaCapsule400 mg/1OralE.R. Squibb & Sons, L.L.C.2009-06-01Not applicableUS flag
DroxiaCapsule200 mg/1OralE.R. Squibb & Sons, L.L.C.2009-06-01Not applicableUS flag
DroxiaCapsule300 mg/1OralE.R. Squibb & Sons, L.L.C.2009-06-01Not applicableUS flag
HydreaCapsule500 mg/1OralE.R. Squibb & Sons, L.L.C.2009-06-01Not applicableUS flag
Hydrea Cap 500mgCapsuleOralBristol Myers Squibb1979-12-31Not applicableCanada flag
HydroxyureaCapsule500 mgOralSanis Health Inc2010-02-252017-07-31Canada flag
SiklosTablet, film coated100 mgOralAddmedica2007-06-29Not applicableEU flag
SiklosTablet, film coated1000 mgOralAddmedica2007-06-29Not applicableEU flag
SiklosTablet, film coated1000 mg/1OralMedunik2018-02-06Not applicableUS flag
SiklosTablet, film coated100 mgOralAddmedica2007-06-29Not applicableEU flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

    Learn more
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Apo-hydroxyureaCapsuleOralApotex Corporation2003-10-22Not applicableCanada flag
HydroxyureaCapsule500 mg/1OralAmerican Health Packaging2008-08-13Not applicableUS flag
HydroxyureaCapsule500 mg/1OralPhysicians Total Care, Inc.2003-04-11Not applicableUS flag00555 0882 02 nlmimage10 9b304da2
HydroxyureaCapsule500 mg/1OralCardinal Health2008-08-12Not applicableUS flag
HydroxyureaCapsule500 mg/1OralGolden State Medical Supply, Inc.1999-02-24Not applicableUS flag49884 0724 01 nlmimage10 2e3b1748
HydroxyureaCapsule500 mg/1OralAvKARE, Inc.2013-07-23Not applicableUS flag
HydroxyureaCapsule500 mg/1OralLeading Pharma, Llc2020-07-09Not applicableUS flag
HydroxyureaCapsule500 mg/1OralREMEDYREPACK INC.2017-12-20Not applicableUS flag
HydroxyureaCapsule500 mg/1OralTeva Pharmaceuticals USA, Inc.1998-10-19Not applicableUS flag0555 088220180907 15195 99tqwx
HydroxyureaCapsule500 mg/1OralMajor Pharmaceuticals1999-02-24Not applicableUS flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

    Learn more

Categories

ATC Codes
L01XX05 — Hydroxycarbamide
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as carboximidic acids and derivatives. These are compounds containing a carboximidic group, with the general formula R-C(=NR1)OR2.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboximidic acids and derivatives
Sub Class
Not Available
Direct Parent
Carboximidic acids and derivatives
Alternative Parents
Organopnictogen compounds / Organooxygen compounds / Imines / Hydrocarbon derivatives
Substituents
Aliphatic acyclic compound / Carboximidic acid derivative / Hydrocarbon derivative / Imine / Organic nitrogen compound / Organic oxygen compound / Organonitrogen compound / Organooxygen compound / Organopnictogen compound
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
one-carbon compound, ureas (CHEBI:44423) / a small molecule (HYDROXY-UREA)

Chemical Identifiers

UNII
X6Q56QN5QC
CAS number
127-07-1
InChI Key
VSNHCAURESNICA-UHFFFAOYSA-N
InChI
InChI=1S/CH4N2O2/c2-1(4)3-5/h5H,(H3,2,3,4)
IUPAC Name
hydroxyurea
SMILES
NC(=O)NO

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 References
Not Available
Human Metabolome Database
HMDB0015140
KEGG Drug
D00341
KEGG Compound
C07044
PubChem Compound
3657
PubChem Substance
46506927
ChemSpider
3530
BindingDB
50017811
RxNav
5552
ChEBI
44423
ChEMBL
CHEMBL467
ZINC
ZINC000008034120
Therapeutic Targets Database
DAP000739
PharmGKB
PA449942
PDBe Ligand
NHY
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Hydroxyurea
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
PDB Entries
2geh / 3ub9
MSDS
Download (75.1 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingTreatmentSickle Cell Anemia / Sickle Cell Disease (SCD)1
4CompletedOtherRenal Function Disorder / Sickle Cell Disease (SCD)1
4CompletedTreatmentDrepanocytic Men Treated by Hydroxyurea for the First Time1
4CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
4CompletedTreatmentThrombocythemia, Hemorrhagic1
4Enrolling by InvitationTreatmentSickle Cell Anemia1
3Active Not RecruitingPreventionSickle Cell Anemia / Sickle Cell Disease (SCD) / Stroke1
3Active Not RecruitingTreatmentEssential Thrombocythemia (ET) / Polycythemia Vera (PV) / Primary Myelofibrosis1
3Active Not RecruitingTreatmentMDS1
3CompletedNot AvailableEssential Thrombocythemia (ET)1

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
  • Amerisource Health Services Corp.
  • Barr Pharmaceuticals
  • Bristol-Myers Squibb Co.
  • Dispensing Solutions
  • Duramed
  • E.R. Squibb and Sons LLC
  • Kaiser Foundation Hospital
  • Liberty Pharmaceuticals
  • Major Pharmaceuticals
  • Medisca Inc.
  • MGI Pharma
  • Murfreesboro Pharmaceutical Nursing Supply
  • Par Pharmaceuticals
  • Pharmaceutical Utilization Management Program VA Inc.
  • Physicians Total Care Inc.
  • Qualitest
  • Roxane Labs
  • United Research Laboratories Inc.
Dosage Forms
FormRouteStrength
CapsuleOral
CapsuleOral200 mg/1
CapsuleOral300 mg/1
CapsuleOral400 mg/1
Capsule500 mg
CapsuleOral500 mg/1
CapsuleOral500 MG
Tablet, film coatedOral100 mg
Tablet, film coatedOral100 mg/1
Tablet, film coatedOral1000 mg
Tablet, film coatedOral1000 mg/1
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.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)133-136U.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 FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
GC-MS Spectrum - GC-MS (3 TMS)GC-MSsplash10-0059-3950000000-0418fbb00ea645e9e0ce
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - GC-MSGC-MSsplash10-0059-3950000000-0418fbb00ea645e9e0ce
GC-MS Spectrum - GC-EI-TOFGC-MSsplash10-0002-0920000000-be691e1a11d76d687cc5
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-03di-9000000000-15e079ef519fdae75dab
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-03di-9000000000-f39d1396b2b03d5846c8
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-01ox-9000000000-b5fb6577ca88b375ebea
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0006-9000000000-6093ebde62cb84552dd0

Targets

Kind
Protein
Organism
Humans
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
Uniprot Name
Ribonucleoside-diphosphate reductase large subunit
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
Humans
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...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Brousseau DC, McCarver DG, Drendel AL, Divakaran K, Panepinto JA: The effect of CYP2D6 polymorphisms on the response to pain treatment for pediatric sickle cell pain crisis. J Pediatr. 2007 Jun;150(6):623-6. doi: 10.1016/j.jpeds.2007.01.049. [PubMed:17517247]
  2. Hydroxyurea - National Toxicology Program - NIH [Link]

Drug created on June 13, 2005 07:24 / Updated on September 17, 2020 23:28

Logo pink
Are you a
new drug developer?
Contact us to learn more about our customized products and solutions.
Logo pink
Stay in the know!
As part of our commitment to providing the most up-to-date drug information, we will be releasing #DrugBankUpdates with our newly added curated drug pages.
#DrugBankUpdates