Hydroxyurea

Identification

Summary

Hydroxyurea is an antimetabolite used to treat sickle cell anemia crisis, resistant chronic myeloid leukemia, and Locally advanced squamous cell carcinomas of the head and neck (excluding the lip).

Brand Names
Droxia, Hydrea, Siklos
Generic Name
Hydroxyurea
DrugBank Accession Number
DB01005
Background

Hydroxyurea is a non-alkylating antineoplastic agent that was first synthesized in 1869 but was not characterized biologically until 1928.5 It was first approved by the FDA in 1998 for the treatment of sickle cell anemia in adults.6 Although clinical evidence on the efficacy of hydroxyurea in certain conditions exists, hydroxyurea is used sparingly in clinical settings, largely due to lack of knowledge and adherence, the need for therapeutic monitoring, and serious side effects of secondary cancer and birth defects.7

Type
Small Molecule
Groups
Approved
Structure
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

Hydroxyurea is indicated to reduce the frequency of painful crises and to reduce the need for blood transfusions in adult and pediatric patients, 2 years of age and older, with sickle cell anemia with recurrent moderate to severe painful crises.8

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofChronic myelogenous leukemia (cml)••••••••••••••••••••• •••••••••••••
Treatment ofEssential thrombocythemia••• •••••
For therapyHead and neck primary squamous cell carcinoma••••••••••••••••••••••••
Treatment ofHypereosinophilic syndrome••• •••••
For therapyLocally advanced squamous cell carcinomas of the head and neck (scchn)•••••••••••••••••••
Associated Therapies
Contraindications & Blackbox Warnings
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Pharmacodynamics

The correlation between hydroxyurea concentrations, reduction of crisis rate, and increase in HbF, is not known.16

Mechanism of action

The precise mechanism by which hydroxyurea produces its antineoplastic effects cannot, at present, be described. However, the reports of various studies in rat and human tissue cultures lend support to the hypothesis that hydroxyurea causes an immediate inhibition of DNA synthesis, by acting as a ribonucleotide reductase inhibitor, without interfering with the synthesis of ribonucleic acid or of protein. Hydroxyurea probably acts by decreasing the rate of conversion of ribonucleotides and deoxyribonucleotides. This effect is particularly apparent in cells with a high rate of proliferation.12 Particularly, hydroxyurea reduces the tyrosyl free radical at the active site of the M2 via a one-electron transfer reaction through the –NH2-OH moiety.5

Three mechanisms have been postulated for the potentiation of the therapeutic effects of irradiation by hydroxyurea on squamous cell (epidermoid) carcinomas of the head and neck. In vitro studies utilizing Chinese hamster cells suggest that hydroxyurea is lethal to normally radioresistant S-stage cells and holds other cells of the cell cycle in the G1 or pre-DNA synthesis stage where they are most susceptible to the effects of irradiation. The third mechanism of action has been theorized on the basis of in vitro studies of HeLa cells: it appears that hydroxyurea, by inhibition of DNA synthesis, hinders the normal repair process of cells damaged but not killed by irradiation, thereby decreasing their survival rate; there is no alteration of RNA and protein syntheses.12

Another proposed mechanism of action of hydroxyurea is the elevation of HbF concentrations in Sickle Cell Disease patients. HbF interferes with the polymerization of HbS (sickle haemoglobin) and thus impedes the sickling of red blood cell. Recently, hydroxyurea has shown to be associated with the generation of nitric oxide, suggesting that nitric oxide stimulates cyclic guanosine monophosphates (cGMP) production, which then activates a protein kinase and increases the production of HbF. Other known pharmacological effects of hydroxycarbamide which may contribute to its beneficial effects in Sickle Cell Disease include decrease of neutrophils, improved deformability of sickled cells, and altered adhesion of red blood cells to the endothelium.11

TargetActionsOrganism
ARibonucleoside-diphosphate reductase large subunit
inhibitor
Humans
Absorption

After oral administration hydroxyurea is readily absorbed from the gastrointestinal tract. Peak plasma concentrations are reached within 2 hours and by 24 hours the serum concentrations are virtually zero. Bioavailability is complete or nearly complete in cancer patients.11

After oral administration of 20 mg/kg of hydroxyurea, a rapid absorption is observed with peak plasma levels of about 30 mg/L occurring after 0.75 and 1.2 h in children and adult patients with sickle cell syndrome, respectively. The total exposure up to 24 h post-dose is 124 mg.h/L in children and adolescents and 135 mg.h/L in adult patients. The oral bioavailability of hydroxyurea is almost complete as assessed in indications other than sickle cell syndrome.13

In a comparative bioavailability study in healthy adult volunteers (n=28), 500 mg of hydroxyurea oral solution was demonstrated to be bioequivalent to the reference 500 mg capsule, with respect to both the peak concentration and area under the curve. There was a statistically significant reduction in time to peak concentration with hydroxyurea oral solution compared to the reference 500 mg capsule (0.5 versus 0.75 hours, p = 0.0467), indicating a faster rate of absorption.[L47137

In a study of children with Sickle Cell Disease, liquid and capsule formulations resulted in similar area under the curve, peak concentrations, and half-life. The largest difference in the pharmacokinetic profile was a trend towards a shorter time to peak concentration following ingestion of the liquid compared with the capsule, but that difference did not reach statistical significance (0.74 versus 0.97 hours, p = 0.14).11

Volume of distribution

Hydroxyurea distributes rapidly throughout the human body, enters the cerebrospinal fluid, appears in peritoneal fluid and ascites, and concentrates in leukocytes and erythrocytes. The estimated volume of distribution of hydroxycarbamide approximates total body water. The volume of distribution following oral dosing of hydroxycarbamide is approximately equal to total body water: adult values of 0.48 – 0.90 L/kg have been reported, whilst in children a population estimate of 0.7 L/kg has been reported.11

Protein binding

The extent of protein binding of hydroxyurea is unknown.11

Metabolism

Up to 60% of an oral dose undergoes conversion through saturable hepatic metabolism and a minor pathway of degradation to acetohydroxamic acid by urease found in intestinal bacteria.9,12

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Route of elimination

A significant fraction of hydroxycarbamide is eliminated by nonrenal (mainly hepatic) mechanisms. In adults, the urinary recovery of unchanged drug is reported to be approximately 37% of the oral dose when renal function is normal. In children, the fraction of hydroxyurea excreted unchanged into the urine comprised about 50%.11

Half-life

In adult cancer patients, hydroxyurea was eliminated with a half-life of approximately 2-3 hours. In a single-dose study in children with Sickle Cell Disease, the mean half-life was reported to be 1.7 hours.11

Clearance

The total body clearance of hydroxyurea in adult patients with Sickle Cell Disease is 0.17 L/h/kg. The respective value in children was similar, 0.22 L/h/kg.11

Adverse Effects
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Toxicity

Oral, mouse: LD50 = 7330 mg/kg; Oral, rat: LD50 = 5760 mg/kg

Hydroxyurea can cause fetal harm based on findings from animal studies and the drug’s mechanism of action. There are no studies on the use of Hydroxyurea in pregnant women and limited available data on SIKLOS use during pregnancy are insufficient to inform drug-associated risks. Drugs that affect DNA synthesis, such as hydroxyurea, may be potential mutagenic agents. In animal reproduction studies, administration of hydroxyurea to pregnant rats and rabbits during organogenesis produced embryotoxic and teratogenic effects at doses 0.8 times and 0.3 times, respectively, the maximum recommended human daily dose on a mg/m² basis. In rats and rabbits, fetal malformations were observed with partially ossified cranial bones, absence of eye sockets, hydrocephaly, bipartite sternebrae, and missing lumbar vertebrae. Embryotoxicity was characterized by decreased fetal viability, reduced live litter sizes, and developmental delays. Advise pregnant women of the potential risk to a fetus.16

Acute mucocutaneous toxicity has been reported in patients receiving hydroxyurea at doses several times above the therapeutic dose. Soreness, violet erythema, edema on palms and soles followed by scaling of hand and feet, severe generalized hyperpigmentation of the skin, and stomatitis have been observed. In patients with sickle cell anemia, neutropenia was reported in isolated cases of hydroxyurea overdose (1.43 times and 8.57 times the maximum recommended dose of 35 mg/kg b.w./day). Monitor blood counts weekly until recovery. Treatment of overdose consists of gastric lavage, followed by symptomatic treatment and control of bone marrow function.16

Conventional long-term studies to evaluate the carcinogenic potential of hydroxyurea have not been performed. However, hydroxyurea is presumed to be a transspecies carcinogen. Intraperitoneal administration of 125 to 250 mg/kg hydroxyurea (about 0.6-1.2 times the maximum recommended human oral daily dose on a mg/m2 basis) thrice weekly for 6 months in female rats increased the incidence of mammary tumors in rats surviving to 18 months compared to control. Hydroxyurea is mutagenic in vitro to bacteria, fungi, protozoa, and mammalian cells. Hydroxyurea is clastogenic in vitro (hamster cells, human lymphoblasts) and in vivo (SCE assay in rodents, mouse micronucleus assay). Hydroxyurea causes the transformation of rodent embryo cells to a tumorigenic phenotype.16

Hydroxyurea administered to male rats at 60 mg/kg /day (about 0.3 times the maximum recommended human daily dose on a mg/m2 basis) produced testicular atrophy, decreased spermatogenesis, and significantly reduced their ability to impregnate females.16

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.
AcenocoumarolThe risk or severity of bleeding can be increased when Acenocoumarol is combined with Hydroxyurea.
AcetaminophenThe risk or severity of methemoglobinemia can be increased when Acetaminophen is combined with Hydroxyurea.
Acetylsalicylic acidThe risk or severity of bleeding can be increased when Acetylsalicylic acid is combined with Hydroxyurea.
Food Interactions
  • Drink plenty of fluids. Drinking extra fluids will help pass more urine to prevent kidney problems and keep the kidneys working well.

Products

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Product Images
International/Other Brands
Litalir (Bristol-Myers Squibb) / Onco-Carbide (Teofarma)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
DroxiaCapsule200 mg/1OralH2-Pharma LLC2009-06-01Not applicableUS flag
DroxiaCapsule400 mg/1OralE.R. Squibb & Sons, L.L.C.2009-06-012025-05-31US flag
DroxiaCapsule300 mg/1OralH2-Pharma LLC2009-06-01Not applicableUS flag
DroxiaCapsule200 mg/1OralE.R. Squibb & Sons, L.L.C.2009-06-012025-03-31US flag
DroxiaCapsule400 mg/1OralH2-Pharma LLC2009-06-01Not applicableUS flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Apo-hydroxyureaCapsule500 mgOralApotex Corporation2003-10-22Not applicableCanada flag
HydroxyureaCapsule500 mg/1OralTeva Pharmaceuticals USA, Inc.1998-10-191998-10-19US flag
HydroxyureaCapsule500 mg/1OralPar Pharmaceutical, Inc.1999-02-24Not applicableUS flag
HydroxyureaCapsule500 mg/1OralCardinal Health 107, LLC1999-02-24Not applicableUS flag
HydroxyureaCapsule500 mg/1OralAmerican Health Packaging2008-09-17Not applicableUS flag

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)
Affected organisms
  • Humans and other mammals

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
  1. Ferrari A, Carobbio A, Masciulli A, Ghirardi A, Finazzi G, De Stefano V, Vannucchi AM, Barbui T: Clinical outcomes under hydroxyurea treatment in polycythemia vera: a systematic review and meta-analysis. Haematologica. 2019 Dec;104(12):2391-2399. doi: 10.3324/haematol.2019.221234. Epub 2019 May 23. [Article]
  2. Cortelazzo S, Finazzi G, Ruggeri M, Vestri O, Galli M, Rodeghiero F, Barbui T: Hydroxyurea for patients with essential thrombocythemia and a high risk of thrombosis. N Engl J Med. 1995 Apr 27;332(17):1132-6. doi: 10.1056/NEJM199504273321704. [Article]
  3. Kim MS, Yu DW, Jung YJ, Kim SW, Chang CH, Kim OL: Long-term follow-up result of hydroxyurea chemotherapy for recurrent meningiomas. J Korean Neurosurg Soc. 2012 Dec;52(6):517-22. doi: 10.3340/jkns.2012.52.6.517. Epub 2012 Dec 31. [Article]
  4. Klion A: Hypereosinophilic syndrome: approach to treatment in the era of precision medicine. Hematology Am Soc Hematol Educ Program. 2018 Nov 30;2018(1):326-331. doi: 10.1182/asheducation-2018.1.326. [Article]
  5. Singh A, Xu YJ: The Cell Killing Mechanisms of Hydroxyurea. Genes (Basel). 2016 Nov 17;7(11):99. doi: 10.3390/genes7110099. [Article]
  6. Strouse JJ, Lanzkron S, Beach MC, Haywood C, Park H, Witkop C, Wilson RF, Bass EB, Segal JB: Hydroxyurea for sickle cell disease: a systematic review for efficacy and toxicity in children. Pediatrics. 2008 Dec;122(6):1332-42. doi: 10.1542/peds.2008-0441. [Article]
  7. Ware RE, Aygun B: Advances in the use of hydroxyurea. Hematology Am Soc Hematol Educ Program. 2009:62-9. doi: 10.1182/asheducation-2009.1.62. [Article]
  8. DailyMed Label: SIKLOS (hydroxyurea) tablets, for oral use [Link]
  9. FDA Approved Drug Products: DROXIA (hydroxyurea) capsules, for oral use [Link]
  10. FDA Approved Drug Products: SIKLOS (hydroxyurea) tablets, for oral use [Link]
  11. EMA Approved Drug Products: Xromi (hydroxycarbamide) solution for oral use [Link]
  12. Health Canada Approved Drug Proucts: APO-HYDROXYUREA (Hydroxyurea) capsules for oral use [Link]
  13. EMA Approved Drug Products: Siklos (hydroxycarbamide) solution for oral use [Link]
  14. Dailymed Label: HYDREA (hydroxyurea) capsule, for oral use [Link]
  15. Hydroxyurea MSDS [Link]
  16. FDA Approved Drug Products: SIKLOS (hydroxyurea) tablets, for oral use (Dec 2023) [Link]
  17. FDA Approved Drug Products: DROXIA (hydroxyurea) capsules, for oral use (Dec 2023) [Link]
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
Hydroxycarbamide
PDB Entries
2geh / 3ub9
MSDS
Download (75.1 KB)

Clinical Trials

Clinical Trials

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
CapsuleOral200 mg/1
CapsuleOral300 mg/1
CapsuleOral400 mg/1
CapsuleOral500 mg
CapsuleOral500.00 mg
Tablet, film coatedOral100 mg
Tablet, film coatedOral1000 mg
CapsuleOral500 mg/1
CapsuleOral
Tablet, film coatedOral100 mg/1
Tablet, film coatedOral1000 mg/1
SolutionOral100 mg/ml
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-MSsplash10-0006-9000000000-725178d2fb4e3ae0a710
GC-MS Spectrum - GC-MSGC-MSsplash10-0059-3950000000-0418fbb00ea645e9e0ce
GC-MS Spectrum - GC-EI-TOFGC-MSsplash10-0002-0920000000-be691e1a11d76d687cc5
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
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-004l-9000000000-2cb93f8279e6cd527621
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0006-9000000000-ab3043a29007f077b446
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0006-9000000000-deefff25aa23efd24fb8
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0006-9000000000-d0aaae6e59e8876360fd
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0006-9000000000-3c1315cf4419fe8cd4a1
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0006-9000000000-14b587fed3bad0f83b1a
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-101.870706
predicted
DarkChem Lite v0.1.0
[M-H]-101.862806
predicted
DarkChem Lite v0.1.0
[M-H]-101.962306
predicted
DarkChem Lite v0.1.0
[M-H]-115.460686
predicted
DeepCCS 1.0 (2019)
[M+H]+101.577106
predicted
DarkChem Lite v0.1.0
[M+H]+102.058306
predicted
DarkChem Lite v0.1.0
[M+H]+102.092506
predicted
DarkChem Lite v0.1.0
[M+H]+117.33379
predicted
DeepCCS 1.0 (2019)
[M+Na]+101.428406
predicted
DarkChem Lite v0.1.0
[M+Na]+101.288706
predicted
DarkChem Lite v0.1.0
[M+Na]+101.417606
predicted
DarkChem Lite v0.1.0
[M+Na]+124.647545
predicted
DeepCCS 1.0 (2019)

Targets

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insights and accelerate drug research.
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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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  5. FDA Approved Drug Products: SIKLOS (hydroxyurea) tablets, for oral use (Dec 2023) [Link]

Enzymes

Kind
Protein
Organism
Bacillus pasteurii
Pharmacological action
No
Actions
Substrate
General Function
Urease activity
Specific Function
Not Available
Gene Name
ureC
Uniprot ID
P41020
Uniprot Name
Urease subunit alpha
Molecular Weight
61397.44 Da
References
  1. FDA Approved Drug Products: DROXIA (hydroxyurea) capsules, for oral use [Link]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Binder
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Naik KM, Kolli DB, Nandibewoor ST: Elucidation of binding mechanism of hydroxyurea on serum albumins by different spectroscopic studies. Springerplus. 2014 Jul 15;3:360. doi: 10.1186/2193-1801-3-360. eCollection 2014. [Article]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent transport of organic anions such as sulfobromophthalein (BSP) and conjugated (taurocholate) and unconjugated (cholate) bile acids (By similarity). Selectively inhibit...
Gene Name
SLCO1A2
Uniprot ID
P46721
Uniprot Name
Solute carrier organic anion transporter family member 1A2
Molecular Weight
74144.105 Da
References
  1. Walker AL, Franke RM, Sparreboom A, Ware RE: Transcellular movement of hydroxyurea is mediated by specific solute carrier transporters. Exp Hematol. 2011 Apr;39(4):446-56. doi: 10.1016/j.exphem.2011.01.004. Epub 2011 Jan 21. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
References
  1. Walker AL, Franke RM, Sparreboom A, Ware RE: Transcellular movement of hydroxyurea is mediated by specific solute carrier transporters. Exp Hematol. 2011 Apr;39(4):446-56. doi: 10.1016/j.exphem.2011.01.004. Epub 2011 Jan 21. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotre...
Gene Name
SLCO1B3
Uniprot ID
Q9NPD5
Uniprot Name
Solute carrier organic anion transporter family member 1B3
Molecular Weight
77402.175 Da
References
  1. Walker AL, Franke RM, Sparreboom A, Ware RE: Transcellular movement of hydroxyurea is mediated by specific solute carrier transporters. Exp Hematol. 2011 Apr;39(4):446-56. doi: 10.1016/j.exphem.2011.01.004. Epub 2011 Jan 21. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Urea transmembrane transporter activity
Specific Function
Specialized low-affinity vasopressin-regulated urea transporter. Mediates rapid transepithelial urea transport across the inner medullary collecting duct and plays a major role in the urinary conce...
Gene Name
SLC14A2
Uniprot ID
Q15849
Uniprot Name
Urea transporter 2
Molecular Weight
101207.965 Da
References
  1. Walker AL, Franke RM, Sparreboom A, Ware RE: Transcellular movement of hydroxyurea is mediated by specific solute carrier transporters. Exp Hematol. 2011 Apr;39(4):446-56. doi: 10.1016/j.exphem.2011.01.004. Epub 2011 Jan 21. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Water transmembrane transporter activity
Specific Function
Urea channel that facilitates transmembrane urea transport down a concentration gradient. A constriction of the transmembrane channel functions as selectivity filter through which urea is expected ...
Gene Name
SLC14A1
Uniprot ID
Q13336
Uniprot Name
Urea transporter 1
Molecular Weight
42527.93 Da
References
  1. Walker AL, Franke RM, Sparreboom A, Ware RE: Transcellular movement of hydroxyurea is mediated by specific solute carrier transporters. Exp Hematol. 2011 Apr;39(4):446-56. doi: 10.1016/j.exphem.2011.01.004. Epub 2011 Jan 21. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Symporter activity
Specific Function
Sodium-ion dependent, low affinity carnitine transporter. Probably transports one sodium ion with one molecule of carnitine. Also transports organic cations such as tetraethylammonium (TEA) without...
Gene Name
SLC22A4
Uniprot ID
Q9H015
Uniprot Name
Solute carrier family 22 member 4
Molecular Weight
62154.48 Da
References
  1. Walker AL, Franke RM, Sparreboom A, Ware RE: Transcellular movement of hydroxyurea is mediated by specific solute carrier transporters. Exp Hematol. 2011 Apr;39(4):446-56. doi: 10.1016/j.exphem.2011.01.004. Epub 2011 Jan 21. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Symporter activity
Specific Function
Sodium-ion dependent, high affinity carnitine transporter. Involved in the active cellular uptake of carnitine. Transports one sodium ion with one molecule of carnitine. Also transports organic cat...
Gene Name
SLC22A5
Uniprot ID
O76082
Uniprot Name
Solute carrier family 22 member 5
Molecular Weight
62751.08 Da
References
  1. Walker AL, Franke RM, Sparreboom A, Ware RE: Transcellular movement of hydroxyurea is mediated by specific solute carrier transporters. Exp Hematol. 2011 Apr;39(4):446-56. doi: 10.1016/j.exphem.2011.01.004. Epub 2011 Jan 21. [Article]

Drug created at June 13, 2005 13:24 / Updated at March 03, 2024 18:31