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Hydroxyurea
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
Structure for Hydroxyurea (DB01005)
- 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.
Target Actions Organism ARibonucleoside-diphosphate reductase large subunit inhibitorHumans - 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.
Drug Interaction Unlock Additional DataAbatacept The risk or severity of adverse effects can be increased when Hydroxyurea is combined with Abatacept. Abciximab The risk or severity of bleeding can be increased when Abciximab is combined with Hydroxyurea. Acebutolol The metabolism of Acebutolol can be decreased when combined with Hydroxyurea. Acenocoumarol The risk or severity of bleeding can be increased when Acenocoumarol is combined with Hydroxyurea. Acetaminophen The metabolism of Acetaminophen can be decreased when combined with Hydroxyurea. Acetylsalicylic acid The risk or severity of bleeding can be increased when Acetylsalicylic acid is combined with Hydroxyurea. Adalimumab The risk or severity of adverse effects can be increased when Adalimumab is combined with Hydroxyurea. Adenovirus type 7 vaccine live The risk or severity of infection can be increased when Adenovirus type 7 vaccine live is combined with Hydroxyurea. Aldesleukin The risk or severity of adverse effects can be increased when Aldesleukin is combined with Hydroxyurea. Alefacept The risk or severity of adverse effects can be increased when Alefacept is combined with Hydroxyurea. Additional Data Available- Extended DescriptionExtended Description
Extended description of the mechanism of action and particular properties of each drug interaction.
Learn more - Severity
- Evidence Level
- ActionAction
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
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Unlock Additional DataDroxia Capsule 400 mg/1 Oral E.R. Squibb & Sons, L.L.C. 2009-06-01 Not applicable US 
Droxia Capsule 200 mg/1 Oral E.R. Squibb & Sons, L.L.C. 2009-06-01 Not applicable US Droxia Capsule 300 mg/1 Oral E.R. Squibb & Sons, L.L.C. 2009-06-01 Not applicable US Hydrea Capsule 500 mg/1 Oral E.R. Squibb & Sons, L.L.C. 2009-06-01 Not applicable US Hydrea Cap 500mg Capsule Oral Bristol Myers Squibb 1979-12-31 Not applicable Canada 
Hydroxyurea Capsule 500 mg Oral Sanis Health Inc 2010-02-25 2017-07-31 Canada Siklos Tablet, film coated 100 mg Oral Addmedica 2007-06-29 Not applicable EU 
Siklos Tablet, film coated 1000 mg Oral Addmedica 2007-06-29 Not applicable EU Siklos Tablet, film coated 1000 mg/1 Oral Medunik 2018-02-06 Not applicable US Siklos Tablet, film coated 100 mg Oral Addmedica 2007-06-29 Not applicable EU Additional Data Available- Application NumberApplication Number
A unique ID assigned by the FDA when a product is submitted for approval by the labeller.
Learn more - Product CodeProduct Code
A governmentally-recognized ID which uniquely identifies the product within its regulatory market.
Learn more
- Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Unlock Additional DataApo-hydroxyurea Capsule Oral Apotex Corporation 2003-10-22 Not applicable Canada Hydroxyurea Capsule 500 mg/1 Oral American Health Packaging 2008-08-13 Not applicable US Hydroxyurea Capsule 500 mg/1 Oral Physicians Total Care, Inc. 2003-04-11 Not applicable US 
Hydroxyurea Capsule 500 mg/1 Oral Cardinal Health 2008-08-12 Not applicable US Hydroxyurea Capsule 500 mg/1 Oral Golden State Medical Supply, Inc. 1999-02-24 Not applicable US 
Hydroxyurea Capsule 500 mg/1 Oral AvKARE, Inc. 2013-07-23 Not applicable US Hydroxyurea Capsule 500 mg/1 Oral Leading Pharma, Llc 2020-07-09 Not applicable US Hydroxyurea Capsule 500 mg/1 Oral REMEDYREPACK INC. 2017-12-20 Not applicable US Hydroxyurea Capsule 500 mg/1 Oral Teva Pharmaceuticals USA, Inc. 1998-10-19 Not applicable US 
Hydroxyurea Capsule 500 mg/1 Oral Major Pharmaceuticals 1999-02-24 Not applicable US Additional Data Available- Application NumberApplication Number
A unique ID assigned by the FDA when a product is submitted for approval by the labeller.
Learn more - Product CodeProduct Code
A governmentally-recognized ID which uniquely identifies the product within its regulatory market.
Learn more
Categories
- ATC Codes
- L01XX05 — Hydroxycarbamide
- Drug Categories
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- Antisickling Agents
- Cytochrome P-450 CYP2D6 Inhibitors
- Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)
- Cytochrome P-450 Enzyme Inhibitors
- Enzyme Inhibitors
- Hematologic Agents
- Immunosuppressive Agents
- Myelosuppressive Agents
- Narrow Therapeutic Index Drugs
- Nucleic Acid Synthesis Inhibitors
- 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
- External Links
- Human Metabolome Database
- HMDB0015140
- KEGG Drug
- D00341
- KEGG Compound
- C07044
- PubChem Compound
- 3657
- PubChem Substance
- 46506927
- ChemSpider
- 3530
- BindingDB
- 50017811
- 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
Phase Status Purpose Conditions Count 4 Active Not Recruiting Treatment Sickle Cell Anemia / Sickle Cell Disease (SCD) 1 4 Completed Other Renal Function Disorder / Sickle Cell Disease (SCD) 1 4 Completed Treatment Drepanocytic Men Treated by Hydroxyurea for the First Time 1 4 Completed Treatment Human Immunodeficiency Virus (HIV) Infections 1 4 Completed Treatment Thrombocythemia, Hemorrhagic 1 4 Enrolling by Invitation Treatment Sickle Cell Anemia 1 3 Active Not Recruiting Prevention Sickle Cell Anemia / Sickle Cell Disease (SCD) / Stroke 1 3 Active Not Recruiting Treatment Essential Thrombocythemia (ET) / Polycythemia Vera (PV) / Primary Myelofibrosis 1 3 Active Not Recruiting Treatment MDS 1 3 Completed Not Available Essential 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
Form Route Strength Capsule Oral Capsule Oral 200 mg/1 Capsule Oral 300 mg/1 Capsule Oral 400 mg/1 Capsule 500 mg Capsule Oral 500 mg/1 Capsule Oral 500 MG Tablet, film coated Oral 100 mg Tablet, film coated Oral 100 mg/1 Tablet, film coated Oral 1000 mg Tablet, film coated Oral 1000 mg/1 - Prices
Unit description Cost Unit Hydroxyurea powder 2.75USD g Hydrea 500 mg capsule 1.49USD capsule Droxia 400 mg capsule 0.97USD capsule Droxia 300 mg capsule 0.94USD capsule Droxia 200 mg capsule 0.91USD capsule Hydroxyurea 500 mg capsule 0.9USD capsule DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 133-136 U.S. Patent 2,705,727. water solubility 1E+006 mg/L (at 25 °C) MERCK INDEX (1996) logP -1.80 HANSCH,C ET AL. (1995) logS 1.12 ADME Research, USCD - Predicted Properties
Property Value Source Water Solubility 269.0 mg/mL ALOGPS logP -1.8 ALOGPS logP -1.4 ChemAxon logS 0.55 ALOGPS pKa (Strongest Acidic) 10.14 ChemAxon pKa (Strongest Basic) -4.9 ChemAxon Physiological Charge 0 ChemAxon Hydrogen Acceptor Count 2 ChemAxon Hydrogen Donor Count 3 ChemAxon Polar Surface Area 75.35 Å2 ChemAxon Rotatable Bond Count 0 ChemAxon Refractivity 14.91 m3·mol-1 ChemAxon Polarizability 5.94 Å3 ChemAxon Number of Rings 0 ChemAxon Bioavailability 1 ChemAxon Rule of Five Yes ChemAxon Ghose Filter No ChemAxon Veber's Rule No ChemAxon MDDR-like Rule No ChemAxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9154 Blood Brain Barrier + 0.9382 Caco-2 permeable - 0.7235 P-glycoprotein substrate Non-substrate 0.8437 P-glycoprotein inhibitor I Non-inhibitor 0.9736 P-glycoprotein inhibitor II Non-inhibitor 0.9946 Renal organic cation transporter Non-inhibitor 0.9697 CYP450 2C9 substrate Non-substrate 0.8063 CYP450 2D6 substrate Non-substrate 0.8363 CYP450 3A4 substrate Non-substrate 0.7784 CYP450 1A2 substrate Non-inhibitor 0.9045 CYP450 2C9 inhibitor Non-inhibitor 0.9077 CYP450 2D6 inhibitor Non-inhibitor 0.927 CYP450 2C19 inhibitor Non-inhibitor 0.9026 CYP450 3A4 inhibitor Non-inhibitor 0.9072 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9778 Ames test AMES toxic 0.8685 Carcinogenicity Non-carcinogens 0.6129 Biodegradation Not ready biodegradable 0.7305 Rat acute toxicity 1.1524 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9846 hERG inhibition (predictor II) Non-inhibitor 0.9715
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
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
- 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]
- 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]
- 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]
- 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
- 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]
- Hydroxyurea - National Toxicology Program - NIH [Link]
Drug created on June 13, 2005 07:24 / Updated on September 17, 2020 23:28
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