Hydroxyurea

Summary

Hydroxyurea (CHEMBL467) is an approved small-molecule DNA synthesis inhibitor (ATC L01XX05) targeting RRM1 and RRM2; indicated across 47 conditions including melanoma and neoplasm.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: L01XX05
• Targets: 2 (RRM1, RRM2)
• Indications: 47 conditions
• Clinical trials: 188
• Chemistry: 76.055 Da · CH4N2O2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL467
Name	Hydroxyurea
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	3657
ChEBI	CHEBI:44423
ATC	L01XX05
Molecular formula	CH4N2O2
Molecular weight	76.055
InChIKey	VSNHCAURESNICA-UHFFFAOYSA-N

SMILES: C(=O)(N)NO

IUPAC name: hydroxyurea

ChEBI definition: A member of the class of ureas that is urea in which one of the hydrogens is replaced by a hydroxy group. An antineoplastic used in the treatment of chronic myeloid leukaemia as well as for sickle-cell disease.

Pharmacological roles (ChEBI): DNA synthesis inhibitor, EC 1.17.4.1 (ribonucleoside-diphosphate reductase) inhibitor, antineoplastic agent, genotoxin, teratogenic agent, radical scavenger, immunomodulator, antimitotic.

Other ChEBI roles (chemical / environmental): antimetabolite.

Also known as: Droxia, Hidroxicarbamida, Hydrea, Hydroxycarbamide, Hydroxyurea, NSC-32065, Siklos, SQ 1089, SQ-1089, Xromi, hydroxy urea, hydroxyurea

Patent coverage: 37,912 distinct patent families (150,394 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 150,393 (100%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
RRM1	ribonucleotide reductase catalytic subunit M1	Inhibition	3.83	100% (common-essential)	P23921
RRM2	ribonucleotide reductase regulatory subunit M2	Inhibition	3.83	99.8% (common-essential)	P31350

Broader ChEMBL bioactivity targets: 11 (assay-derived). Sample: Prelamin-A/C, RecQ-like DNA helicase BLM, Inositol monophosphatase 1, Peripheral myelin protein 22, Thyrotropin receptor, Carbonic anhydrase 2, Nuclear factor NF-kappa-B p105 subunit, Cytochrome P450 3A4, Carbonic anhydrase 9, Urease subunit alpha/Urease subunit beta.

Bioactivity

ChEMBL activities: 2 potent at pChembl ≥ 5 of 15 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
NFKB1	5.5	Potency	3162	nM	CHEMBL_ACT_3675778
NFKB1	5.5	Potency	3162	nM	CHEMBL_ACT_4588960

Target pathways

Aggregated over 2 target gene(s): RRM1, RRM2.

Top Reactome pathways

3 total, by targets touching each:

Pathway	Targets	Genes
Interconversion of nucleotide di- and triphosphates	2	RRM1, RRM2
G1/S-Specific Transcription	1	RRM2
Transcriptional Regulation by E2F6	1	RRM2

Dominant GO biological processes

GO term	Targets
DNA repair	2
ribonucleoside diphosphate metabolic process	2
deoxyribonucleotide biosynthetic process	2
2’-deoxyribonucleotide biosynthetic process	2
protein heterotetramerization	2
positive regulation of G1/S transition of mitotic cell cycle	2
DNA synthesis involved in DNA repair	1
pyrimidine nucleobase metabolic process	1
mitochondrial DNA replication	1
male gonad development	1
response to ionizing radiation	1
positive regulation of G2/M transition of mitotic cell cycle	1
cell proliferation in forebrain	1
retina development in camera-type eye	1
positive regulation of G0 to G1 transition	1

Indications & clinical

Indications

47 indications (6 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
melanoma	4	MONDO:0005105	EFO:0000756
neoplasm	4	MONDO:0005070	EFO:0000616
chronic myeloid leukemia	4	MONDO:0011996	EFO:0000339
squamous cell carcinoma	4	MONDO:0005096	EFO:0000707
sickle cell disease	4	MONDO:0011382	MONDO:0011382
head and neck squamous cell carcinoma	4	MONDO:0010150	EFO:0000181
leukemia	3	MONDO:0005059	EFO:0000565
essential thrombocythemia	3	MONDO:0005029	EFO:0000479
acquired polycythemia vera	3	MONDO:0009891	EFO:0002429
myelodysplastic syndrome	3	MONDO:0018881	EFO:0000198
glioblastoma	3	MONDO:0018177	EFO:0000519
acute promyelocytic leukemia	3	MONDO:0012883	EFO:0000224
carcinoma	3	MONDO:0004993	EFO:0000313
stroke disorder	3	MONDO:0005098	EFO:0000712
HIV infectious disease	3	MONDO:0005109	EFO:0000764
primary myelofibrosis	3	MONDO:0009692	EFO:0002430
hematologic disorder	3	MONDO:0005570	HP:0001871
laryngeal neoplasm	3	MONDO:0021071	EFO:0003817
paranasal sinus neoplasm	3	MONDO:0005289	EFO:0003866
oral cavity cancer	3	MONDO:0005515	EFO:0005570
pharynx cancer	3	MONDO:0005517	EFO:0005577
hereditary hemochromatosis	3	MONDO:0006507	EFO:1000642
astrocytoma (excluding glioblastoma)	3	MONDO:0019781	EFO:0000272
inherited hemoglobinopathy	3	MONDO:0019050	MONDO:0044348
acute myeloid leukemia	2	MONDO:0018874	EFO:0000222
lymphoma	2	MONDO:0005062	EFO:0000574
head and neck cancer	2	MONDO:0005627	EFO:0006859
gliosarcoma	2	MONDO:0016681	EFO:1001465
beta thalassemia	2	MONDO:0019402	Orphanet:848
spinal muscular atrophy	2	MONDO:0001516	EFO:0008525
central nervous system neoplasm	2	MONDO:0006130	EFO:1000158
gastric neoplasm	2	MONDO:0021085	MONDO:0001056
acute lymphoblastic leukemia	2	MONDO:0004967	EFO:0000220
desmoid tumor	2	MONDO:0007608	EFO:0009907
thalassemia	2	MONDO:0000984	EFO:1001996
multiple sclerosis	2	MONDO:0005301	MONDO:0005301
meningioma	2	MONDO:0016642	MONDO:0016642
fibromatosis	2	MONDO:0005031	EFO:0000497
lung neoplasm	1	MONDO:0021117	MONDO:0008903
paraganglioma	1	MONDO:0000448	EFO:1000453
pulmonary hypertension	0	MONDO:0005149	MONDO:0005149

6 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 188.

Phase distribution

Phase	Trials
PHASE2	70
PHASE3	34
Not specified	25
PHASE1	23
PHASE1/PHASE2	17
PHASE2/PHASE3	9
PHASE4	7
EARLY_PHASE1	3

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06526117	PHASE4	RECRUITING	Stroke Prevention in Nigeria 2 Trial
NCT00005018	PHASE4	COMPLETED	Safety and Effectiveness of a Combination Anti-HIV Drug Treatment
NCT00202644	PHASE4	COMPLETED	A Study of Anagrelide and Hydroxyurea in High-Risk Essential Thrombocythemia Patients
NCT02149537	PHASE4	COMPLETED	Risk Clinical Stratification of Sickle Cell Disease in Nigeria, Assessment of Efficacy/Safety of Hydroxyurea Treatment
NCT02522104	PHASE4	COMPLETED	Evaluation of the Impact of Renal Function on the Pharmacokinetics of SIKLOS ® (DARH)
NCT05853458	PHASE4	TERMINATED	Evaluation of HU-resistance in Adult Patients With Polycythemia Vera Who Meet PV-AIM Predictors
NCT06299670	PHASE4	UNKNOWN	Efficacy of Combination of Hdroxyurea and Thalidomide Over Either Hydroxyurea or Thalidomide Alone in the Treatment of Transfusion Dependent Thalassemia in Children: A Quasi-Randomised Clinical Trial
NCT04116502	PHASE3	RECRUITING	MITHRIDATE: Ruxolitinib Versus Hydroxycarbamide or Interferon as First Line Therapy in High Risk Polycythemia Vera
NCT05285917	PHASE3	RECRUITING	Promoting Utilization and Safety of Hydroxyurea Using Precision in Africa
NCT06093672	PHASE3	RECRUITING	Study on Efficacy and Safety of Givinostat Versus Hydroxyurea in Patients With Polycythemia Vera
NCT06456346	PHASE3	RECRUITING	Bomedemstat vs Hydroxyurea for Essential Thrombocythemia (MK-3543-007)
NCT00000586	PHASE3	COMPLETED	Multicenter Study of Hydroxyurea in Patients With Sickle Cell Anemia (MSH)
NCT00002230	PHASE3	COMPLETED	A Randomized, Placebo-Controlled Study of the Safety and Efficacy of Efavirenz, Didanosine, and Stavudine in Combination With or Without Hydroxyurea in Antiretroviral Naive or Experienced HIV-Infected Patients
NCT00002771	PHASE3	UNKNOWN	Chemotherapy, Interferon, and Bone Marrow Transplantation in Treating Patients With Chronic Myelogenous Leukemia
NCT00002868	PHASE3	COMPLETED	Interferon-alfa With or Without Chemotherapy and Peripheral Stem Cell Transplantation in Treating Patients With Newly Diagnosed Chronic Myelogenous Leukemia
NCT00002869	PHASE3	UNKNOWN	Interferon Alfa in Treating Patients With Newly Diagnosed Chronic Myelogenous Leukemia
NCT00004933	PHASE3	TERMINATED	Homoharringtonine Compared With Hydroxyurea for Chronic Myelogenous Leukemia That Has Not Responded to Interferon Alfa
NCT00005823	PHASE3	COMPLETED	Intensive Compared With Nonintensive Chemotherapy in Treating Older Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome
NCT00006400	PHASE3	COMPLETED	Hydroxyurea to Prevent Organ Damage in Children With Sickle Cell Anemia
NCT00025402	PHASE3	UNKNOWN	Chemotherapy and Biological Therapy With or Without Bone Marrow or Peripheral Stem Cell Transplant in Treating Patients With Chronic Myelogenous Leukemia
NCT00055874	PHASE3	COMPLETED	Imatinib Mesylate With or Without Interferon Alfa or Cytarabine Compared With Interferon Alfa Followed by Donor Stem Cell Transplant in Treating Patients With Newly Diagnosed Chronic Phase Chronic Myelogenous Leukemia
NCT00117572	PHASE3	COMPLETED	Docetaxel Based Chemotherapy Plus or Minus Induction Chemotherapy to Decrease Events in Head and Neck Cancer (DeCIDE)
NCT00122980	PHASE3	TERMINATED	Stroke With Transfusions Changing to Hydroxyurea
NCT00154375	PHASE3	COMPLETED	Study of Imatinib Mesylate in Combination With Hydroxyurea Versus Hydroxyurea Alone as an Oral Therapy in Patients With Temozolomide Resistant Progressive Glioblastoma
NCT00180973	PHASE3	UNKNOWN	PHASE III TRIAL COMPARING, NEOADJUVANT CHEMOTHERAPY FOLLOWED BY STANDARD RADIOTHERAPY VERSUS THE SAME NEOADJUVANT CHEMOTHERAPY FOLLOWED BY STANDARD RADIOTHERAPY ASSOCIATED WITH DAILY HYDROXYUREA IN THE TREATMENT OF LOCALLY ADVANCED UNDIFFERENTIATED CARCINOMA NASOPHARYNGEAL TYPE.
NCT00485511	PHASE2/PHASE3	COMPLETED	A Trial of Hydroxyurea in Spinal Muscular Atrophy
NCT01065038	PHASE3	COMPLETED	Anagrelide vs. Hydroxyurea - Efficacy and Tolerability Study in Patients With Essential Thrombocythaemia
NCT01103583	PHASE2/PHASE3	TERMINATED	Hydroxyurea in Primary Progressive Multiple Sclerosis
NCT01211938	PHASE2/PHASE3	COMPLETED	Trial Comparing Two Protocols of re Irradiation in an Irradiated Area for Carcinoma of the Upper Aerodigestive Tract
NCT01259856	PHASE3	COMPLETED	Randomized Trial of Pegylated Interferon Alfa-2a Versus Hydroxyurea in Polycythemia Vera (PV) and Essential Thrombocythemia (ET)
NCT01387763	PHASE3	COMPLETED	A Study of Low Dose Interferon Alpha Versus Hydroxyurea in Treatment of Chronic Myeloid Neoplasms
NCT01425307	PHASE3	TERMINATED	Transcranial Doppler (TCD) With Transfusions Changing to Hydroxyurea
NCT01531387	PHASE3	TERMINATED	Sparing Conversion to Abnormal TCD (Transcranial Doppler) Elevation (SCATE)
NCT01624038	PHASE2/PHASE3	UNKNOWN	Therapeutic Effect and Safety of Combined Hydroxyurea With Recombinant Human Erythropoietin.
NCT01632904	PHASE3	COMPLETED	Randomized Switch Study From Hydroxyurea to Ruxolitinib for RELIEF of Polycythemia Vera Symptoms: The Relief Study
NCT01645124	PHASE3	TERMINATED	Large-scale Trial Testing the Intensity of CYTOreductive Therapy in Polycythemia Vera (PV)
NCT01949805	PHASE3	COMPLETED	Pegylated Interferon Alpha-2b Versus Hydroxyurea in Polycythemia Vera
NCT01976416	PHASE3	COMPLETED	Novel Use Of Hydroxyurea in an African Region With Malaria
NCT02214407	PHASE3	COMPLETED	Randomized Phase III Study of Decitabine +/- Hydroxyurea (HY) Versus HY in Advanced Proliferative CMML
NCT02899169	PHASE3	UNKNOWN	Treatment of Non-high-risk Acute Promyelocytic Leukemia (APL) With Realgar-Indigo Naturalis Formula (RIF)

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 2 clinical and 21 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

4 molecules share ≥1 primary target. Top 4 by shared-target count:

Molecule	Source	Status	Shared targets
TRIAPINE	ChEMBL	Phase 3	RRM1, RRM2
Clofarabine	PubChem	Approved	RRM1, RRM2
Fludarabine	PubChem	Approved	RRM1, RRM2
Gemcitabine	PubChem	Approved	RRM1, RRM2