Hydroxyurea

Details

Stereochemistry	ACHIRAL
Molecular Formula	CH4N2O2
Molecular Weight	76.0547
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NC(=O)NO

InChI

InChIKey=VSNHCAURESNICA-UHFFFAOYSA-N

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

HIDE SMILES / InChI

Description
Sources: https://www.pdr.net/drug-summary/Hydrea-hydroxyurea-888 | https://www.ncbi.nlm.nih.gov/pubmed/24839362

Hydroxyurea is an oral antimetabolite; inhibits ribonucleotide reductase and DNA synthesis. It is used for resistant chronic myeloid leukemia, locally advanced squamous cell carcinomas of the head and neck (excluding lip) in combination with concurrent chemoradiation, and to reduce the frequency of painful crises and the need for blood transfusions in patients with sickle cell anemia with recurrent moderate to severe painful crises. Hydroxyurea, a myelosuppressive agent, is the only effective drug proven to reduce the frequency of painful episodes. It raises the level of HbF and the haemoglobin level. It usually decreases the rate of painful episodes by 50%. It was first tested in sickle cell disease in 1984. It also decreases the rate of ACS episodes and blood transfusions by ~50 % in adults. It was developed as an anticancer drug and has been used to treat myeloproliferative syndromes-leukemia, melanoma, and ovarian cancer. It was approved for use by FDA in adults. Side effects includes neutropenia, bone marrow suppression, elevation of hepatic enzymes, anorexia, nausea, vomiting and infertility.

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Ribonucleotide reductase 8 Target ID: CHEMBL3301398 Sources: https://www.ncbi.nlm.nih.gov/pubmed/1641648 \| https://www.ncbi.nlm.nih.gov/pubmed/18367739	Inhibitor 8504

Conditions

Condition	Modality	Targets	Highest Phase	Product
Sickle cell anemia 12 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/016295s049s050lbl.pdf	Primary		Approved 8583	DROXIA Approved Use DROXIA is an antimetabolite indicated to reduce the frequency of painful crises and to reduce the need for blood transfusions in patients with sickle cell anemia with recurrent moderate to severe painful crises Launch Date 1967

C_max

Value	Dose	Co-administered	Analyte	Population
793.75 μM EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/9473217	2000 mg single, oral dose: 2000 mg route of administration: Oral experiment type: SINGLE co-administered:		HYDROXYUREA plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
3934 μM × h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/9473217	2000 mg single, oral dose: 2000 mg route of administration: Oral experiment type: SINGLE co-administered:		HYDROXYUREA plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
3.32 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/9473217	2000 mg single, oral dose: 2000 mg route of administration: Oral experiment type: SINGLE co-administered:		HYDROXYUREA plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252	inhibitor 2438	inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1741 BCRP 910 OATP1B1 1079 OATP1B3 961 BSEP 550 MRP2 499 MRP3 246 MRP4 290 CYP1A2 2153 CYP2A6 879 CYP2C19 2057 CYP2E1 1060	OATP1B3 435 OATP1A2 67 OATP1B1 503 OCTN1 55 OCTN2 59 CYP 303	P-gp 301

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP2D6 2546	inhibitor 4027 Sources: https://bioinformatics.charite.de/transformer/index.php?site=fullinfo&cname=000127071, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1978168/, https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwyODkiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMNDY3In19	likely [IC50 >10 uM]	yes (pharmacogenomic study) Comment: Of the 73 children completing the study, 42 had reduced-functioning alleles; 82% of the 27 children taking hydoxyurea had reduced-functioning alleles, versus 47% of 36 those with mild disease (P < .05). Sources: https://bioinformatics.charite.de/transformer/index.php?site=fullinfo&cname=000127071, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1978168/, https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwyODkiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMNDY3In19
CYP3A4 2633	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/17180388/, https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNDAiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMNDY3In19	no [Activation 39.8107 uM]
CYP1A2 2333	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzMzU2IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDQ2NyJ9fQ%3D%3D	no [IC50 >10 uM]
CYP2A6 911	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw1MjgyIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDQ2NyJ9fQ%3D%3D	no [IC50 >10 uM]
CYP2C19 2141	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNjIyIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDQ2NyJ9fQ%3D%3D	no [IC50 >10 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzMzk3IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDQ2NyJ9fQ%3D%3D	no [IC50 >10 uM]
CYP2E1 1146	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw1MjgxIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDQ2NyJ9fQ%3D%3D	no [IC50 >10 uM]
BSEP 554	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/23956101/	no [IC50 >133 uM]
MRP2 625	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/23956101/	no [IC50 >133 uM]
MRP3 326	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/23956101/	no [IC50 >133 uM]
MRP4 345	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/23956101/	no [IC50 >133 uM]
BCRP 985	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/17180388/	no
P-gp 1932	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/17180388/	no
OATP1B1 1095	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/23571415/	yes
OATP1B3 970	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/23571415/	yes
P-gp 1932	inducer 1966 Sources: https://bioinformatics.charite.de/transformer/index.php?site=fullinfo&cname=000127071, https://pubmed.ncbi.nlm.nih.gov/1550597/	yes

Drug as victim

Target	Modality	Activity
CYP 303	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/19817872/	no
OATP1A2 67	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/21256917/	weak
OATP1B1 503	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/21256917/	weak
OCTN1 55	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/21256917/	weak
OCTN2 59	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/21256917/	weak
OATP1B3 435	substrate 4014 Sources: https://bioinformatics.charite.de/transformer/index.php?site=fullinfo&cname=000127071, https://pubmed.ncbi.nlm.nih.gov/21256917/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwyNDAiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMNDY3In19

PubMed

Title	Date	PubMed
Reduction of telomerase activity in human liver cancer cells by a histone deacetylase inhibitor.	2001-06	11319763
Involvement of pRB-related p107 protein in the inhibition of S phase progression in response to genotoxic stress.	2001-05-18	11278582
ATM-dependent phosphorylation of human Rad9 is required for ionizing radiation-induced checkpoint activation.	2001-05-11	11278446
Skin and nail changes in children with sickle cell anemia receiving hydroxyurea therapy.	2001-05	11312437
Role of petasin in the potential anti-inflammatory activity of a plant extract of petasites hybridus.	2001-04-15	11286996
Cell cycle expression of histone genes in Trypanosoma cruzi.	2001-04-06	11295175
Concomitant infusional paclitaxel and fluorouracil, oral hydroxyurea, and hyperfractionated radiation for locally advanced squamous head and neck cancer.	2001-04-01	11283128
Stroke in hemoglobin (SD) sickle cell disease with moyamoya: successful hydroxyurea treatment after cerebrovascular bypass surgery.	2001-04-01	11264186
In vitro cytotoxic effects of a tyrosine kinase inhibitor STI571 in combination with commonly used antileukemic agents.	2001-04-01	11264164
The Saccharomyces cerevisiae phosphotyrosyl phosphatase activator proteins are required for a subset of the functions disrupted by protein phosphatase 2A mutations.	2001-04-01	11262194
Stroke prevention and treatment in sickle cell disease.	2001-04	11295986
Cutaneous adverse reactions to hydroxyurea in patients with sickle cell disease.	2001-04	11295927
Chromosomal aberrations in lymphocytes of employees in transformer and generator production exposed to electromagnetic fields and mineral oil.	2001-04	11255210
The anti-malarial artesunate is also active against cancer.	2001-04	11251172
A new molecular role for iron in regulation of cell cycling and differentiation of HL-60 human leukemia cells: iron is required for transcription of p21(WAF1/CIP1) in cells induced by phorbol myristate acetate.	2001-04	11241357
Cell cycle-related changes in regulatory volume decrease and volume-sensitive chloride conductance in mouse fibroblasts.	2001-04	11241350
Incidence of pancreatitis in HIV-infected patients receiving nucleoside reverse transcriptase inhibitor drugs.	2001-03-30	11316999
Increased ribonucleotide reductase activity in hydroxyurea-resistant mosquito cells.	2001-03-29	11276057
N-Aminoindoline derivatives as inhibitors of 5-lipoxygenase.	2001-03-26	11277534
Osteoclast differentiation factor modulates cell cycle machinery and causes a delay in s phase progression in RAW264 cells.	2001-03-23	11264004
Topoisomerase IV, alone, unknots DNA in E. coli.	2001-03-15	11274059
The BARD1-CstF-50 interaction links mRNA 3' end formation to DNA damage and tumor suppression.	2001-03-09	11257228
Bloom helicase is involved in DNA surveillance in early S phase in vertebrate cells.	2001-03-08	11313858
Management of patients with essential thrombocythemia: current concepts and perspectives.	2001-03	11317966
Efficacy and safety of hydroxyurea in patients with essential thrombocythemia.	2001-03	11317964
[Hydroxyurea--is it a harmless drug in Vaquez disease?]].	2001-03	11317962
Prognostic factors and current practice in treatment of myelofibrosis with myeloid metaplasia: an update anno 2000.	2001-03	11317960
Myeloproliferative syndromes. Current opinions from the European Hematology Association Working Group on Myeloproliferative Disorders.	2001-03	11317958
Muco-cutaneous changes during long-term therapy with hydroxyurea in chronic myeloid leukaemia.	2001-03	11298103
Hydrogenosome morphological variation induced by fibronectin and other drugs in Trichomonas vaginalis and Tritrichomonas foetus.	2001-03	11293569
Clinical predictors of health-related quality of life depend on asthma severity.	2001-03	11282767
Limbal stem cell deficiency arising from systemic chemotherapy.	2001-03	11277104
Localised chronic eyedlid disease resulting from long term hydroxyurea therapy.	2001-03	11277103
Prognostic impact of bone marrow erythropoietic precursor cells and myelofibrosis at diagnosis of Ph1+ chronic myelogenous leukaemia--a multicentre study on 495 patients.	2001-03	11260078
The Saccharomyces cerevisiae MUM2 gene interacts with the DNA replication machinery and is required for meiotic levels of double strand breaks.	2001-03	11238403
Dynamics of seminal plasma HIV-1 decline after antiretroviral treatment.	2001-02-16	11273229
Clinical and hematological responses to hydroxyurea in Sicilian patients with Hb S/beta-thalassemia.	2001-02	11300353
Hydroxyurea promotes the reduction of spontaneous BFU-e to normal levels in SS and S/beta thalassemic patients.	2001-02	11300342
Replication and G2 checkpoints: their response to caffeine.	2001-02	11289610
The predictive value of vascular risk factors and gender for the development of thrombotic complications in essential thrombocythemia.	2001-02	11261328
Induction of unscheduled DNA synthesis in hairless mouse epidermis by 8-methoxypsoralen plus ultraviolet A (PUVA).	2001-02	11255790
A compromised yeast RNA polymerase II enhances UV sensitivity in the absence of global genome nucleotide excision repair.	2001-02	11254132
The biology and treatment of chronic myelogenous leukemia.	2001-01	11271979
A novel genetic screen identifies checkpoint-defective alleles of Schizosaccharomyces pombe chk1.	2001-01	11270571
Modulation of ara-CTP levels by fludarabine and hydroxyurea in leukemic cells.	2001-01	11243402
Chronic neutrophilic leukemia (CNL): a clinical, pathologic and cytogenetic study.	2001-01	11243396
Current management in polycythemia vera.	2001-01	11242599
[Low-dose cytosine-arabinoside (Ara-C) therapy for chronic myeloid leukemia].	2001	11317537
Body composition in women with sickle cell disease.	2001	11289248
Systematic review of combination antiretroviral therapy with didanosine plus hydroxyurea: a partial solution to Africa's HIV/AIDS problem?	2001	11285159

Patents

Sample Use Guides

In Vivo Use Guide

Usual Adult Dose for Chronic Myelogenous Leukemia 15 mg/kg/day orally as a single dose Usual Adult Dose for Head and Neck Cancer 15 mg/kg/day orally as a single dose Usual Adult Dose for Sickle Cell Anemia 15 mg/kg orally once a day; increase 5 mg/kg/day every 12 weeks Maximum dose: 35 mg/kg/day Usual Pediatric Dose for Sickle Cell Anemia 2 years and older: 20 mg/kg orally once a day; increase 5 mg/kg/day every 8 weeks or if a painful crisis occurs; increase dosing only if blood counts are in the acceptable range; do not increase dosing if myelosuppression occurs; if blood counts are considered toxic, discontinue therapy until hematologic recovery Duration of therapy: Give until mild myelosuppression (absolute neutrophil count 2000/microliter to 4000/microliter) is achieved, up to 35 mg/kg/day Maximum dose: 35 mg/kg/day

Route of Administration: Oral

Name

Type

Language

Hydroxyurea

Official Name

English

HYDROXYCARBAMIDE

Preferred Name

English

HYDROXYUREA [HSDB]

Common Name

English

SIKLOS

Brand Name

English

Hydroxycarbamide [WHO-DD]

Common Name

English

SQ 1089

Code

English

HYDREA

Brand Name

English

HYDROXYCARBAMIDE [EMA EPAR]

Common Name

English

XROMI

Brand Name

English

HYDROXYUREA [VANDF]

Common Name

English

SQ-1089

Code

English

UREA, HYDROXY-

Systematic Name

English

hydroxycarbamide [INN]

Common Name

English

HYDROXYUREA [IARC]

Common Name

English

HYDROXYUREA [USP-RS]

Common Name

English

HYDROXYUREA [USP MONOGRAPH]

Common Name

English

DROXIA

Brand Name

English

HYDROXYCARBAMIDE [EP MONOGRAPH]

Common Name

English

HYDROXYCARBAMIDE [JAN]

Common Name

English

NSC-32065

Code

English

HYDROXYUREA [MI]

Common Name

English

HYDROXYUREA [ORANGE BOOK]

Common Name

English

HYDROXYUREA [USAN]

Common Name

English

HYDROXYCARBAMIDE [MART.]

Common Name

English

Classification Tree Code System Code

WHO-ESSENTIAL MEDICINES LIST

8.2