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Record Information

Version

5.0

Status

Expected but not Quantified

Creation Date

2012-09-06 15:16:51 UTC

Update Date

2023-02-21 17:18:24 UTC

HMDB ID

HMDB0015140

Secondary Accession Numbers

HMDB15140

Metabolite Identification

Common Name

Hydroxyurea

Description

Hydroxyurea, also known as hydroxycarbamide or hydrea, 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. Hydroxyurea is a drug which is used for management of melanoma, resistant chronic myelocytic leukemia, and recurrent, metastatic, or inoperable carcinoma of the ovary and sickle-cell anemia. Hydroxyurea is an extremely weak basic (essentially neutral) compound (based on its pKa). Due to its chemical properties hydroxyurea was explored as an antisickling agent in the treatment of hematological conditions. Hydroxyurea is a potentially toxic compound. It has been found to be superior to anagrelide for the control of ET.Sickle-cell disease (increases production of fetal hemoglobin that then interferes with the hemoglobin polymerisation as well as by reducing white blood cells that contribute to the general inflammatory state in sickle cell patients.)Second line treatment for psoriasis (slows down the rapid division of skin cells)PsoriasisSystemic mastocytosisChronic myelogenous leukemia (largely replaced by imatinib, but still in use for its cost-effectiveness)Reported side-effects are: neurological reactions (e.g., headache, dizziness, drowsiness, disorientation, hallucinations, and convulsions), nausea, vomiting, diarrhea, constipation, mucositis, anorexia, stomatitis, bone marrow toxicity (dose-limiting toxicity; may take 7–21 days to recover after the drug has been discontinued), megaloblastic anemia, thrombocytopenia, bleeding, hemorrhage, gastrointestinal ulceration and perforation, immunosuppression, leukopenia, alopecia (hair loss), skin rashes (e.g., maculopapular rash), erythema, pruritus, vesication or irritation of the skin and mucous membranes, pulmonary edema, abnormal liver enzymes, creatinine and blood urea nitrogen. It is on the World Health Organization's List of Essential Medicines, the safest and most effective medicines needed in a health system. Hydroxyurea has many pharmacological applications under the Medical Subject Headings classification system:Antineoplastic Agents – Substances that inhibit or prevent the proliferation of neoplasms.

Structure

MOL 3D MOL SDF 3D SDF PDB 3D PDB SMILES InChI

View in JSmol View Stereo Labels

Synonyms

Value	Source
Carbamohydroxamic acid	ChEBI
Carbamohydroximic acid	ChEBI
Carbamoyl oxime	ChEBI
Carbamyl hydroxamate	ChEBI
Hidroxicarbamida	ChEBI
Hydrea	ChEBI
Hydroxycarbamid	ChEBI
Hydroxycarbamide	ChEBI
Hydroxycarbamidum	ChEBI
Hydroxyharnstoff	ChEBI
N-Carbamoylhydroxylamine	ChEBI
N-HYDROXYUREA	ChEBI
Oxyurea	ChEBI
Droxia	Kegg
Carbamohydroxamate	Generator
Carbamohydroximate	Generator
Carbamyl hydroxamic acid	Generator
Carbamohydroxyamic acid	HMDB
HU	HMDB
Hydroxicarbamidum	HMDB
Hydroxycarbamine	HMDB
Hydroxylurea	HMDB
Idrossicarbamide	HMDB
Oncocarbide	HMDB

Chemical Formula

CH₄N₂O₂

Average Molecular Weight

76.0547

Monoisotopic Molecular Weight

76.027277382

IUPAC Name

hydroxyurea

Traditional Name

hydroxyurea

CAS Registry Number

127-07-1

SMILES

NC(=O)NO

InChI Identifier

InChI=1S/CH4N2O2/c2-1(4)3-5/h5H,(H3,2,3,4)

InChI Key

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.

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

Substituents

Carboximidic acid derivative
Organic nitrogen compound
Organic oxygen compound
Organopnictogen compound
Hydrocarbon derivative
Organooxygen compound
Organonitrogen compound
Imine
Aliphatic acyclic compound

Molecular Framework

Aliphatic acyclic compounds

External Descriptors

one-carbon compound (CHEBI:44423 )
ureas (CHEBI:44423 )
a small molecule (HYDROXY-UREA )

Ontology

Physiological effect

Not Available

Disposition

Biological location

Non-excretory biofluid

Biofluid or Excreta

Blood (PMID: 21059682)

Excreta

Biofluid or Excreta

Urine (PMID: 21059682)

Cellular substructure

Cytoplasm (HMDB: HMDB0015140)
Membrane (HMDB: HMDB0015140)

Source

Exogenous

Exogenous (HMDB: HMDB0015140)

Process

Not Available

Role

Not Available

Physical Properties

State

Solid

Experimental Molecular Properties

Property	Value	Reference
Melting Point	142 - 146 °C	Not Available
Boiling Point	Not Available	Not Available
Water Solubility	269 g/L	Not Available
LogP	-1.6	Not Available

Experimental Chromatographic Properties

Not Available

Predicted Molecular Properties

Property	Value	Source
Water Solubility	269 g/L	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	Yes	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	No	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	No	ChemAxon

Predicted Chromatographic Properties

Predicted Collision Cross Sections

Predictor	Adduct Type	CCS Value (Å²)	Reference
DarkChem	[M+H]+	112.711	31661259
DarkChem	[M-H]-	105.842	31661259
DeepCCS	[M+H]+	117.334	30932474
DeepCCS	[M-H]-	115.461	30932474
DeepCCS	[M-2H]-	150.746	30932474
DeepCCS	[M+Na]+	124.648	30932474
AllCCS	[M+H]+	125.4	32859911
AllCCS	[M+H-H2O]+	121.1	32859911
AllCCS	[M+NH4]+	129.5	32859911
AllCCS	[M+Na]+	130.7	32859911
AllCCS	[M-H]-	125.8	32859911
AllCCS	[M+Na-2H]-	131.5	32859911
AllCCS	[M+HCOO]-	137.8	32859911

Predicted Kovats Retention Indices

Underivatized

Metabolite	SMILES	Kovats RI Value	Column Type	Reference
Hydroxyurea	NC(=O)NO	2304.8	Standard polar	33892256
Hydroxyurea	NC(=O)NO	1046.2	Standard non polar	33892256
Hydroxyurea	NC(=O)NO	1212.5	Semi standard non polar	33892256

Derivatized

Derivative Name / Structure	SMILES	Kovats RI Value	Column Type	Reference
Hydroxyurea,1TMS,isomer #1	C[Si](C)(C)NC(=O)NO	1274.1	Semi standard non polar	33892256
Hydroxyurea,1TMS,isomer #1	C[Si](C)(C)NC(=O)NO	1191.4	Standard non polar	33892256
Hydroxyurea,1TMS,isomer #1	C[Si](C)(C)NC(=O)NO	2083.6	Standard polar	33892256
Hydroxyurea,1TMS,isomer #2	C[Si](C)(C)N(O)C(N)=O	1213.4	Semi standard non polar	33892256
Hydroxyurea,1TMS,isomer #2	C[Si](C)(C)N(O)C(N)=O	1134.9	Standard non polar	33892256
Hydroxyurea,1TMS,isomer #2	C[Si](C)(C)N(O)C(N)=O	1949.3	Standard polar	33892256
Hydroxyurea,2TMS,isomer #1	C[Si](C)(C)N(C(=O)NO)[Si](C)(C)C	1329.9	Semi standard non polar	33892256
Hydroxyurea,2TMS,isomer #1	C[Si](C)(C)N(C(=O)NO)[Si](C)(C)C	1221.4	Standard non polar	33892256
Hydroxyurea,2TMS,isomer #1	C[Si](C)(C)N(C(=O)NO)[Si](C)(C)C	1651.3	Standard polar	33892256
Hydroxyurea,2TMS,isomer #2	C[Si](C)(C)NC(=O)N(O)[Si](C)(C)C	1271.2	Semi standard non polar	33892256
Hydroxyurea,2TMS,isomer #2	C[Si](C)(C)NC(=O)N(O)[Si](C)(C)C	1238.0	Standard non polar	33892256
Hydroxyurea,2TMS,isomer #2	C[Si](C)(C)NC(=O)N(O)[Si](C)(C)C	1684.9	Standard polar	33892256
Hydroxyurea,3TMS,isomer #1	C[Si](C)(C)N(O)C(=O)N([Si](C)(C)C)[Si](C)(C)C	1372.0	Semi standard non polar	33892256
Hydroxyurea,3TMS,isomer #1	C[Si](C)(C)N(O)C(=O)N([Si](C)(C)C)[Si](C)(C)C	1296.1	Standard non polar	33892256
Hydroxyurea,3TMS,isomer #1	C[Si](C)(C)N(O)C(=O)N([Si](C)(C)C)[Si](C)(C)C	1516.1	Standard polar	33892256
Hydroxyurea,1TBDMS,isomer #1	CC(C)(C)[Si](C)(C)NC(=O)NO	1477.0	Semi standard non polar	33892256
Hydroxyurea,1TBDMS,isomer #1	CC(C)(C)[Si](C)(C)NC(=O)NO	1302.9	Standard non polar	33892256
Hydroxyurea,1TBDMS,isomer #1	CC(C)(C)[Si](C)(C)NC(=O)NO	2096.8	Standard polar	33892256
Hydroxyurea,1TBDMS,isomer #2	CC(C)(C)[Si](C)(C)N(O)C(N)=O	1383.4	Semi standard non polar	33892256
Hydroxyurea,1TBDMS,isomer #2	CC(C)(C)[Si](C)(C)N(O)C(N)=O	1304.2	Standard non polar	33892256
Hydroxyurea,1TBDMS,isomer #2	CC(C)(C)[Si](C)(C)N(O)C(N)=O	2059.3	Standard polar	33892256
Hydroxyurea,2TBDMS,isomer #1	CC(C)(C)[Si](C)(C)N(C(=O)NO)[Si](C)(C)C(C)(C)C	1711.7	Semi standard non polar	33892256
Hydroxyurea,2TBDMS,isomer #1	CC(C)(C)[Si](C)(C)N(C(=O)NO)[Si](C)(C)C(C)(C)C	1592.3	Standard non polar	33892256
Hydroxyurea,2TBDMS,isomer #1	CC(C)(C)[Si](C)(C)N(C(=O)NO)[Si](C)(C)C(C)(C)C	1742.2	Standard polar	33892256
Hydroxyurea,2TBDMS,isomer #2	CC(C)(C)[Si](C)(C)NC(=O)N(O)[Si](C)(C)C(C)(C)C	1685.1	Semi standard non polar	33892256
Hydroxyurea,2TBDMS,isomer #2	CC(C)(C)[Si](C)(C)NC(=O)N(O)[Si](C)(C)C(C)(C)C	1575.8	Standard non polar	33892256
Hydroxyurea,2TBDMS,isomer #2	CC(C)(C)[Si](C)(C)NC(=O)N(O)[Si](C)(C)C(C)(C)C	1818.0	Standard polar	33892256
Hydroxyurea,3TBDMS,isomer #1	CC(C)(C)[Si](C)(C)N(O)C(=O)N([Si](C)(C)C(C)(C)C)[Si](C)(C)C(C)(C)C	1993.3	Semi standard non polar	33892256
Hydroxyurea,3TBDMS,isomer #1	CC(C)(C)[Si](C)(C)N(O)C(=O)N([Si](C)(C)C(C)(C)C)[Si](C)(C)C(C)(C)C	1909.8	Standard non polar	33892256
Hydroxyurea,3TBDMS,isomer #1	CC(C)(C)[Si](C)(C)N(O)C(=O)N([Si](C)(C)C(C)(C)C)[Si](C)(C)C(C)(C)C	1859.1	Standard polar	33892256

Spectra

GC-MS Spectra

Spectrum Type	Description	Splash Key	Deposition Date	Source	View
Experimental GC-MS	GC-MS Spectrum - Hydroxyurea GC-MS (3 TMS)	splash10-0059-3950000000-0418fbb00ea645e9e0ce	2014-06-16	HMDB team, MONA, MassBank	View Spectrum
Experimental GC-MS	GC-MS Spectrum - Hydroxyurea GC-MS (Non-derivatized)	splash10-0059-3950000000-0418fbb00ea645e9e0ce	2017-09-12	HMDB team, MONA, MassBank	View Spectrum
Experimental GC-MS	GC-MS Spectrum - Hydroxyurea GC-EI-TOF (Non-derivatized)	splash10-0002-0920000000-be691e1a11d76d687cc5	2017-09-12	HMDB team, MONA, MassBank	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - Hydroxyurea GC-MS (Non-derivatized) - 70eV, Positive	splash10-0006-9000000000-725178d2fb4e3ae0a710	2017-09-01	Wishart Lab	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - Hydroxyurea GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	Wishart Lab	View Spectrum

MS/MS Spectra

Spectrum Type	Description	Splash Key	Deposition Date	Source	View
Experimental LC-MS/MS	LC-MS/MS Spectrum - Hydroxyurea LC-ESI-QQ , positive-QTOF	splash10-03di-9000000000-15e079ef519fdae75dab	2017-09-14	HMDB team, MONA	View Spectrum
Experimental LC-MS/MS	LC-MS/MS Spectrum - Hydroxyurea LC-ESI-QQ , positive-QTOF	splash10-03di-9000000000-f39d1396b2b03d5846c8	2017-09-14	HMDB team, MONA	View Spectrum
Experimental LC-MS/MS	LC-MS/MS Spectrum - Hydroxyurea LC-ESI-QQ , positive-QTOF	splash10-01ox-9000000000-b5fb6577ca88b375ebea	2017-09-14	HMDB team, MONA	View Spectrum
Experimental LC-MS/MS	LC-MS/MS Spectrum - Hydroxyurea LC-ESI-QQ , positive-QTOF	splash10-0006-9000000000-6093ebde62cb84552dd0	2017-09-14	HMDB team, MONA	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Hydroxyurea 10V, Positive-QTOF	splash10-004i-9000000000-5f85466dc663205c60f9	2016-08-03	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Hydroxyurea 20V, Positive-QTOF	splash10-056r-9000000000-fb233b42b45077d2475d	2016-08-03	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Hydroxyurea 40V, Positive-QTOF	splash10-06tf-9000000000-868a329446e04867fc56	2016-08-03	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Hydroxyurea 10V, Negative-QTOF	splash10-004i-9000000000-6245f3456e3558782716	2016-08-03	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Hydroxyurea 20V, Negative-QTOF	splash10-0006-9000000000-722afb6d05d2ca0794f5	2016-08-03	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Hydroxyurea 40V, Negative-QTOF	splash10-0006-9000000000-f6792fcc64ed7bdb2466	2016-08-03	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Hydroxyurea 10V, Positive-QTOF	splash10-004i-9000000000-fbd92a2a1457de08f558	2021-10-11	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Hydroxyurea 20V, Positive-QTOF	splash10-01r6-9000000000-ff7708ba70751a23d1eb	2021-10-11	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Hydroxyurea 40V, Positive-QTOF	splash10-0006-9000000000-fd9f25340762315b4515	2021-10-11	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Hydroxyurea 10V, Negative-QTOF	splash10-0006-9000000000-90726b17dc36e29c5299	2021-10-11	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Hydroxyurea 20V, Negative-QTOF	splash10-0006-9000000000-90726b17dc36e29c5299	2021-10-11	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Hydroxyurea 40V, Negative-QTOF	splash10-0006-9000000000-90726b17dc36e29c5299	2021-10-11	Wishart Lab	View Spectrum

IR Spectra

Spectrum Type	Description	Deposition Date	Source	View
Predicted IR Spectrum	IR Ion Spectrum (Predicted IRIS Spectrum, Adduct: [M-H]-)	2023-02-03	FELIX lab	View Spectrum
Predicted IR Spectrum	IR Ion Spectrum (Predicted IRIS Spectrum, Adduct: [M+H]+)	2023-02-03	FELIX lab	View Spectrum
Predicted IR Spectrum	IR Ion Spectrum (Predicted IRIS Spectrum, Adduct: [M+Na]+)	2023-02-03	FELIX lab	View Spectrum

Biological Properties

Cellular Locations

Cytoplasm
Membrane

Biospecimen Locations

Blood
Urine

Tissue Locations

Not Available

Pathways

Not Available

Name	SMPDB/PathBank	KEGG

Normal Concentrations

Biospecimen	Status	Value	Age	Sex	Condition	Reference	Details
Blood	Expected but not Quantified	Not Quantified	Not Available	Not Available	Taking drug identified by DrugBank entry DB01005	21059682	details
Urine	Expected but not Quantified	Not Quantified	Not Available	Not Available	Taking drug identified by DrugBank entry DB01005	21059682	details

Abnormal Concentrations

Not Available

Predicted Concentrations

Biospecimen	Value	Original age	Original sex	Original condition	Comments
Blood	0.000 uM	Adult (>18 years old)	Both	Normal	Predicted based on drug qualities
Blood	0.000 umol/mmol creatinine	Adult (>18 years old)	Both	Normal	Predicted based on drug qualities

Associated Disorders and Diseases

Disease References

None

Associated OMIM IDs

None

External Links

DrugBank ID

DB01005

Phenol Explorer Compound ID

Not Available

FooDB ID

Not Available

KNApSAcK ID

Not Available

Chemspider ID

3530

KEGG Compound ID

C07044

BioCyc ID

HYDROXY-UREA

BiGG ID

Not Available

Wikipedia Link

Hydroxyurea

METLIN ID

Not Available

PubChem Compound

3657

PDB ID

NHY

ChEBI ID

44423

Food Biomarker Ontology

Not Available

VMH ID

Not Available

MarkerDB ID

Not Available

Good Scents ID

Not Available

References

Synthesis Reference

Not Available

Material Safety Data Sheet (MSDS)

Download (PDF)

General References

Not Available

Enzymes

Enzyme Details

1. Ribonucleoside-diphosphate reductase large subunit

General function:: Involved in oxidation reduction
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

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 ]

Enzyme Details

2. Cytochrome P450 2D6

General function:: Involved in monooxygenase 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

References

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 ]

Showing metabocard for Hydroxyurea (HMDB0015140)

MOL for HMDB0015140 (Hydroxyurea)

3D MOL for HMDB0015140 (Hydroxyurea)

3D SDF for HMDB0015140 (Hydroxyurea)

3D-SDF for HMDB0015140 (Hydroxyurea)

PDB for HMDB0015140 (Hydroxyurea)

3D PDB for HMDB0015140 (Hydroxyurea)

SMILES for HMDB0015140 (Hydroxyurea)

INCHI for HMDB0015140 (Hydroxyurea)

Structure for HMDB0015140 (Hydroxyurea)

3D Structure for HMDB0015140 (Hydroxyurea)

Predicted Collision Cross Sections

Predicted Kovats Retention Indices

Underivatized

Derivatized

GC-MS Spectra

MS/MS Spectra

IR Spectra

Enzymes

References

References