ETANIDAZOLE

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C7H10N4O4
Molecular Weight	214.1787
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OCCNC(=O)CN1C=CN=C1[N+]([O-])=O

InChI

InChIKey=WCDWBPCFGJXFJZ-UHFFFAOYSA-N

InChI=1S/C7H10N4O4/c12-4-2-8-6(13)5-10-3-1-9-7(10)11(14)15/h1,3,12H,2,4-5H2,(H,8,13)

HIDE SMILES / InChI

Molecular Formula	C7H10N4O4
Molecular Weight	214.1787
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/8398704 | https://adisinsight.springer.com/drugs/800000828

Etanidazole (also known as Radinyl) is a 2-nitroimidazole with radiosensitizing properties. Etanidazole exerts its therapeutic action by depleting glutathione and inhibiting glutathione S-transferase, thus enhancing the anticancer effects of radiation therapy. Etanidazole was tested in Phase III clinical trials in patients with advanced head and neck cancer, however, its development was stopped. A fluorinated etanidazole (EF5) may also be useful as an imaging agent for identification of hypoxic, drug-resistant regions of primary tumors and metastases.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Glutathione-S-transferase 2 Target ID: Glutathione-S-transferase Sources: https://www.ncbi.nlm.nih.gov/pubmed/8398704	Inhibitor 8504

Conditions

Condition	Modality	Targets	Highest Phase	Product
Advanced head and neck cancer 2 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9308928	Primary		Phase III 665	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
287 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2522918	2 g/m² single, intravenous dose: 2 g/m² route of administration: Intravenous experiment type: SINGLE co-administered:		ETANIDAZOLE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
2.55 mM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1826961	4 g/m² single, intravenous dose: 4 g/m² route of administration: Intravenous experiment type: SINGLE co-administered:		ETANIDAZOLE serum	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
5.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2522918	2 g/m² single, intravenous dose: 2 g/m² route of administration: Intravenous experiment type: SINGLE co-administered:		ETANIDAZOLE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252	inhibitor 2438	inhibitor 2507

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OATP1B3 961 CYP1A2 2153 OATP1B1 1079	P-gp 2052

Drug as perpetrator

Target	Modality	Activity
CYP2C19 2141	activator 342 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/899#sid=11112677	no [Activation 5.0119 uM]
CYP1A2 2333	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/410#sid=11112677	no
CYP2C9 2497	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/883#sid=11112677	no
CYP2D6 2546	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/891#sid=11112677	no
CYP3A4 2633	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/885#sid=11112677	no
OATP1B1 1095	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/23571415/	yes [Inhibition 10 uM]
OATP1B3 970	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/23571415/	yes [Inhibition 10 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 2052	substrate 4014 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=144204150	no

Sourcing

Vendor/Aggregator	ID	URL
AKOS	AKOS028109842	http://akoscompounds.de/catalogue/AKosSamplesiSSretrieval.php?GUID=4e4caa52-3dca-4da0-b75a-caeae59e1096&IDNUMBERS=AKOS028109842
BOC Sciences	22668-01-5	http://www.bocsci.com/description.asp?cas=22668-01-5
Compound Cloud	3276
eMolecules	33507364	https://orderbb.emolecules.com/search/#?query=33507364
Enamine	BBV-45084632	http://www.enaminestore.com/catalog/BBV-45084632
Hairui	HR144737	http://www.hairuichem.com/en/product/search.do?q=HR144737
Lab Network	LN01310035	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01310035
MuseChem	R043807	https://www.musechem.com/product/R043807.html
NCI Plated 2007	301467

PubMed

Title	Date	PubMed
Biodistribution and dosimetry of (18)F-EF5 in cancer patients with preliminary comparison of (18)F-EF5 uptake versus EF5 binding in human glioblastoma.	2010-11	20585774
Stereotactic ablative radiotherapy should be combined with a hypoxic cell radiosensitizer.	2010-10-01	20832663
Voltammetry of hypoxic cells radiosensitizer etanidazole radical anion in water.	2010-06	19733129
Inhibitor of DNA binding/differentiation 2 induced by hypoxia promotes synovial fibroblast-dependent osteoclastogenesis.	2009-12	19950294
A fast radiotherapy paradigm for anal cancer with volumetric modulated arc therapy (VMAT).	2009-10-25	19852856
Atrasentan (ABT-627) enhances perfusion and reduces hypoxia in a human tumor xenograft model.	2009-10	19717985
A Novel Docetaxel-Loaded Poly (ε-Caprolactone)/Pluronic F68 Nanoparticle Overcoming Multidrug Resistance for Breast Cancer Treatment.	2009-09-16	20652101
Immunohistochemical detection of changes in tumor hypoxia.	2009-03-15	19251089
Imaging and analytical methods as applied to the evaluation of vasculature and hypoxia in human brain tumors.	2008-12	19138031
18F-EF5: a new PET tracer for imaging hypoxia in head and neck cancer.	2008-12	18997048
Noninvasive molecular imaging of hypoxia in human xenografts: comparing hypoxia-induced gene expression with endogenous and exogenous hypoxia markers.	2008-10-15	18922936
Regulation of cell survival and death signals induced by oxidative stress.	2008-09	18818753
Changes in tumor hypoxia induced by mild temperature hyperthermia as assessed by dual-tracer immunohistochemistry.	2008-08	18538874
Importance of antibody concentration in the assessment of cellular hypoxia by flow cytometry: EF5 and pimonidazole.	2008-06	18494550
Pharmaceutical particle engineering via spray drying.	2008-05	18040761
A phase I-B trial of the radiosensitizer: etanidazole (SR-2508) with radiosurgery for the treatment of recurrent previously irradiated primary brain tumors or brain metastases (RTOG Study 95-02).	2008-04	18342381
In vivo measurement of the hypoxia marker EF5 in Shionogi tumours using (19)F magnetic resonance spectroscopy.	2008-03	18300024
Hyperbaric oxygen reduces tissue hypoxia and hypoxia-inducible factor-1 alpha expression in focal cerebral ischemia.	2008-03	18239183
Imaging of tumor hypoxia to predict treatment sensitivity.	2008	18991711
Patterns and levels of hypoxia in head and neck squamous cell carcinomas and their relationship to patient outcome.	2007-11-15	17967299
The radiosensitizing effect of doranidazole on human colorectal cancer cells exposed to high doses of irradiation.	2007-10-06	17919337
Radiosensitization of paclitaxel, etanidazole and paclitaxel+etanidazole nanoparticles on hypoxic human tumor cells in vitro.	2007-09	17509678
Radiosensitization by the combination of SR-2508 and paclitaxel in hypoxic human tumor cells in vitro.	2007-05	17420623
In situ oxygen utilization in the rat intervertebral disc.	2007-03	17331178
In vivo performance of implantable biodegradable preparations delivering Paclitaxel and Etanidazole for the treatment of glioma.	2007-02	17067667
Identifying and targeting hypoxia in head and neck cancer: a brief overview of current approaches.	2007	17848296
Motexafin gadolinium injection for the treatment of brain metastases in patients with non-small cell lung cancer.	2007	17722515
New methods for direct delivery of chemotherapy for treating brain tumors.	2006-12	17940624
Oxygen levels in normal and previously irradiated human skin as assessed by EF5 binding.	2006-12	16810299
Detection of tumour hypoxia: comparison between EF5 adducts and [18F]EF3 uptake on an individual mouse tumour basis.	2006-05	16523307
EF5 binding and clinical outcome in human soft tissue sarcomas.	2006-03-01	16458778
Immunomodulatory effects of etanercept in an experimental model of spinal cord injury.	2006-03	16303916
MCT-4, A511/Basigin and EF5 expression patterns during early chick cardiomyogenesis indicate cardiac cell differentiation occurs in a hypoxic environment.	2006-01	16110503
Significance of hypoxia in malignant glioma. Re: Evans et al. Hypoxia is important in the biology and aggression of human glial brain tumors. Clin Cancer Res 2004;10:8177-84.	2005-05-15	15897599
Etanidazole in pH-sensitive liposomes: design, characterization and in vitro/in vivo anti-Trypanosoma cruzi activity.	2005-04-18	15820407
Stabilization of the retinal vascular network by reciprocal feedback between blood vessels and astrocytes.	2005-04	15790963
Hypoxia is important in the biology and aggression of human glial brain tumors.	2004-12-15	15623592
Utility of 19F MRS detection of the hypoxic cell marker EF5 to assess cellular hypoxia in solid tumors.	2004-12	15588883
HER-2/neu overexpression increases the viable hypoxic cell population within solid tumors without causing changes in tumor vascularization.	2004-11	15561777
Hypoxia and Photofrin uptake in the intraperitoneal carcinomatosis and sarcomatosis of photodynamic therapy patients.	2004-07-15	15269134
Quality of life of men treated with brachytherapies for prostate cancer.	2004-06-15	15198803
In vivo evaluation of [18F]fluoroetanidazole as a new marker for imaging tumour hypoxia with positron emission tomography.	2004-06-01	15150578
Acute hypoxia enhances spontaneous lymph node metastasis in an orthotopic murine model of human cervical carcinoma.	2004-03-15	15026343
Role of myocardial hypoxia in the remodeling of the embryonic avian cardiac outflow tract.	2004-03-15	15013795
In vitro activity of Etanidazole against the protozoan parasite Trypanosoma cruzi.	2004-03	15250482
Pneumocystis carinii is resistant to imidazole antifungal agents.	1994-08	7986021
Combined-modality therapy of esophageal cancer with radiotherapy, etanidazole, and cisplatin-fluorouracil, with or without surgery: neurotoxicity, other toxicities and outcome.	1994-06-15	8005812
Phase I/pharmacokinetic/biochemical study of the nitroimadazole hypoxic cell sensitiser SR2508 (etanidazole) in combination with cyclophosphamide.	1993-10	8398704
Enhancement in the aerobic toxicity of misonidazole and SR-2508 by buthionine sulfoximine and 4-hydroxypyrazole: the role of hydrogen peroxide.	1986-07	2943713
Oncogenic transformation systems involving mammalian cells in vitro to determine the relative risks of different treatment modalities.	1984-12	6515665

Patents

Sample Use Guides

In Vivo Use Guide

Etanidazole is given at a dose of 2.0 g/m(2), three times per week for 5.5 weeks in 17 doses up to a total dose of 34 g/m(2). The drug is dissolved in saline and infused i.v., over 10 to 15 min. Radiotherapy is to begin 30 to 60 min after the start of the Etanidazole infusion.

Route of Administration: Intravenous

In Vitro Use Guide

Human leukemia cell lines HL60 and MOLT-4 were treated with 10 mM etanidazole by incubating cells (10(6) ml(-1)) in growth medium at 37 Celsius for 1 h before X-irradiation (15 Gy). The treatment of cells with etanidazole enhanced X-ray-induced apoptosis and the ladder-like DNA fragmentation under the hypoxic conditions.

Substance Class	Chemical Created by `admin` on `Wed Apr 02 12:46:16 GMT 2025` Edited by `admin` on `Wed Apr 02 12:46:16 GMT 2025`
Record UNII	30DKA3Q1HL
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

RADINYL

Preferred Name

English

ETANIDAZOLE

Official Name

English

ETANIDAZOLE [MART.]

Common Name

English

N-(2-Hydroxyethyl)-2-nitroimidazole-1-acetamide

Systematic Name

English

NSC-301467

Code

English

etanidazole [INN]

Common Name

English

SR 2508

Code

English

SR-2508

Code

English

ETANIDAZOLE [USAN]

Common Name

English

ETANIDAZOLE [MI]

Common Name

English

1H-IMIDAZOLE-1-ACETAMIDE, N-(2-HYDROXYETHYL)-2-NITRO-

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C798