Misonidazole

Investigational

Details

Stereochemistry	RACEMIC
Molecular Formula	C7H11N3O4
Molecular Weight	201.1799
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=OBBCSXFCDPPXOL-UHFFFAOYSA-N

InChI=1S/C7H11N3O4/c1-14-5-6(11)4-9-3-2-8-7(9)10(12)13/h2-3,6,11H,4-5H2,1H3

HIDE SMILES / InChI

Description
Sources: https://www.cancer.gov/publications/dictionaries/cancer-drug?cdrid=39504 | https://www.ncbi.nlm.nih.gov/pubmed/24375829 | https://www.ncbi.nlm.nih.gov/pubmed/2799816 | https://www.ncbi.nlm.nih.gov/pubmed/3663461

Misonidazole is a nitroimidazole with radiosensitizing and antineoplastic properties. Exhibiting high electron affinity, misonidazole induces the formation of free radicals and depletes radioprotective thiols, thereby sensitizing hypoxic cells to the cytotoxic effects of ionizing radiation. This single-strand breaks in DNA induced by this agent result in the inhibition of DNA synthesis. The drug also possesses a substantial cytotoxic effect, independent of radiation, which is selectively expressed in hypoxic cells. Misonidazole may be cytotoxic to the normal hypoxic tissues in the human body, making this became a major concern in the clinical application of the drug. Misonidazole leads to strand breaks in cellular DNA and those cells which fail to survive also fail to repair these strand breaks. Misonidazole depletes intracellular glutathione and is more toxic in glutathione depleted cells.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
DNA 282 Target ID: CHEMBL2311221 Sources: https://www.ncbi.nlm.nih.gov/pubmed/1345928 \| https://www.ncbi.nlm.nih.gov/pubmed/397941 \| https://www.ncbi.nlm.nih.gov/pubmed/6168271 \| https://www.researchgate.net/publication/279935665	Interacts 323

Conditions

Condition	Modality	Highest Phase	Product
Glioblastoma 66 Sources: https://clinicaltrials.gov/ct2/show/NCT00902577	Diagnostic	Phase II 1147	Unknown Approved Use Unknown
Sarcoma 14 Sources: https://clinicaltrials.gov/ct2/show/NCT01169350	Diagnostic	Phase II 1147	Unknown Approved Use Unknown
Cervical cancer 40 Sources: https://clinicaltrials.gov/ct2/show/NCT00559377	Diagnostic	Phase II 1147	Unknown Approved Use Unknown
Non-small cell lung cancer 211 Sources: https://clinicaltrials.gov/ct2/show/NCT01507428	Diagnostic	Phase II 1147	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
31.3 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6698564	600 mg/m² single, oral dose: 600 mg/m² route of administration: Oral experiment type: SINGLE co-administered:		MISONIDAZOLE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
125 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6698564	3 g/m² single, oral dose: 3 g/m² route of administration: Oral experiment type: SINGLE co-administered:		MISONIDAZOLE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
348.5 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6698564	600 mg/m² single, oral dose: 600 mg/m² route of administration: Oral experiment type: SINGLE co-administered:		MISONIDAZOLE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
2150 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6698564	3 g/m² single, oral dose: 3 g/m² route of administration: Oral experiment type: SINGLE co-administered:		MISONIDAZOLE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
18 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6698564	3 g/m² single, oral dose: 3 g/m² route of administration: Oral experiment type: SINGLE co-administered:		MISONIDAZOLE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FASTED

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
GSTP1-1 1 P-gp 1741	P450R 1

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1932	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1347076#sid=99360758	no
GSTP1-1 1	inhibitor 4027 Sources: https://www.researchgate.net/publication/271643181_Cancer_Stem_Cells_and_Multiple_Drug_Resistance_in_Breast_Cancer	yes

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
P450R 1	substrate 4014 Sources: https://link.springer.com/chapter/10.1007/978-1-4684-7284-4_8	yes

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY519463	https://www.001chemical.com/chem/13551-87-6
AA Blocks	AA009HRT	https://www.aablocks.com/goods/Goods/detail?id=AA009HRT
Ambinter	Amb22483314	http://www.ambinter.com/reference/22483314
Aurora Fine Chemicals LLC	A17.944.401	http://online.aurorafinechemicals.com/info?ID=A17.944.401
BLD Pharm	BD265540	http://www.bldpharm.com/products/13551-87-6.html
BOC Sciences	13551-87-6	https://www.bocsci.com/misonidazole-cas-13551-87-6-item-65236.html
Chemspace	CSSB00009888890	https://chem-space.com/CSSB00009888890
eNovation Chemicals	D668852	https://www.enovationchem.com/ProductDetails.asp?ProductID=D668852
Lab Network	LN01288629	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01288629
Molcore	MC519463	https://www.molcore.com/product/13551-87-6
MolPort	MolPort-006-120-523	https://www.molport.com/shop/molecule-link/MolPort-006-120-523
MuseChem	R028891	https://www.musechem.com/product/R028891.html
Sigma-Aldrich	PH002757_ALDRICH	https://www.sigmaaldrich.com/catalog/product/aldrich/ph002757
Smolecule	S535510	http://www.smolecule.com/products/s535510
THE BioTek	bt-275291	https://www.thebiotek.com/product/inhibitors/bt-275291

PubMed

Title	Date	PubMed
Fluorine-18-labeled fluoromisonidazole positron emission and computed tomography-guided intensity-modulated radiotherapy for head and neck cancer: a feasibility study.	2008-01-01	17869020
Tumor hypoxia imaging in orthotopic liver tumors and peritoneal metastasis: a comparative study featuring dynamic 18F-MISO and 124I-IAZG PET in the same study cohort.	2008-01	17786438
Hypoxia positron emission tomography imaging with 18f-fluoromisonidazole.	2007-11	17920352
Hypertabastic survival model.	2007-10-26	17963492
Interventions for preventing oral mucositis for patients with cancer receiving treatment.	2007-10-17	17943748
[Molecular design of hypoxic tumor cell-targeting drugs and imaging probes].	2007-10	18051384
Altered calcium homeostasis in motor neurons following AMPA receptor but not voltage-dependent calcium channels' activation in a genetic model of amyotrophic lateral sclerosis.	2007-10	17706428
Experimental hypoxia is a potent stimulus for radiotracer uptake in vitro: comparison of different tumor cells and primary endothelial cells.	2007-08-28	17400370
pO polarography, contrast enhanced color duplex sonography (CDS), [18F] fluoromisonidazole and [18F] fluorodeoxyglucose positron emission tomography: validated methods for the evaluation of therapy-relevant tumor oxygenation or only bricks in the puzzle of tumor hypoxia?	2007-06-28	17598907
In vivo 19F magnetic resonance spectroscopy and chemical shift imaging of tri-fluoro-nitroimidazole as a potential hypoxia reporter in solid tumors.	2007-06-15	17575240
A model of reoxygenation dynamics of head-and-neck tumors based on serial 18F-fluoromisonidazole positron emission tomography investigations.	2007-06-01	17398015
Canadian recommendations for the treatment of glioblastoma multiforme.	2007-06	17593983
Hypoxia-imaging with (18)F-Misonidazole and PET: changes of kinetics during radiotherapy of head-and-neck cancer.	2007-06	17543402
In vivo molecular imaging biomarkers: clinical pharmacology's new "PET"?	2007-06	17505491
A robotic synthesis of [18F]fluoromisonidazole ([18F]FMISO).	2007-06	17379530
Hypoxia dose painting by numbers: a planning study.	2007-05-01	17448882
The influence of tumor oxygenation on hypoxia imaging in murine squamous cell carcinoma using [64Cu]Cu-ATSM or [18F]Fluoromisonidazole positron emission tomography.	2007-04	17332926
Imaging of brain hypoxia in permanent and temporary middle cerebral artery occlusion in the rat using 18F-fluoromisonidazole and positron emission tomography: a pilot study.	2007-04	17033692
Whole brain radiotherapy for brain metastases from breast cancer: estimation of survival using two stratification systems.	2007-03-26	17386108
Imaging tumoral hypoxia: oxygen concentrations and beyond.	2007-03	17447439
Motexafin gadolinium injection for the treatment of brain metastases in patients with non-small cell lung cancer.	2007	17722515
Lack of correlation of hypoxic cell fraction and angiogenesis with glucose metabolic rate in non-small cell lung cancer assessed by 18F-Fluoromisonidazole and 18F-FDG PET.	2006-12	17138734
FDG--a marker of tumour hypoxia? A comparison with [18F]fluoromisonidazole and pO2-polarography in metastatic head and neck cancer.	2006-12	16841141
A model to simulate tumour oxygenation and dynamic [18F]-Fmiso PET data.	2006-11-21	17068369
PET imaging of tumour hypoxia.	2006-10-31	17114063
From anatomical to biological target volumes: the role of PET in radiation treatment planning.	2006-10-31	17114062
Tumor hypoxia imaging with [F-18] fluoromisonidazole positron emission tomography in head and neck cancer.	2006-09-15	17000677
Tumor hypoxia imaging.	2006-09-15	17000656
Combined uptake of [18F]FDG and [18F]FMISO correlates with radiation therapy outcome in head-and-neck cancer patients.	2006-08	16920211
Imaging hypoxia after oxygenation-modification: comparing [18F]FMISO autoradiography with pimonidazole immunohistochemistry in human xenograft tumors.	2006-08	16905213
Characterization of fluoromisonidazole binding in stroke.	2006-07	16763190
Ionizing radiation antagonizes tumor hypoxia induced by antiangiogenic treatment.	2006-06-01	16740778
Radiosensitizers in cervical cancer. Cisplatin and beyond.	2006-05-08	16722549
Prognostic significance of [18F]-misonidazole positron emission tomography-detected tumor hypoxia in patients with advanced head and neck cancer randomly assigned to chemoradiation with or without tirapazamine: a substudy of Trans-Tasman Radiation Oncology Group Study 98.02.	2006-05-01	16648512
Evaluation of hypoxic cell radio-sensitizers in terms of radio-sensitizing and repair-inhibiting potential. Dependency on p53 status of tumor cells and the effects on intratumor quiescent cells.	2006-04-20	16619533
Interventions for preventing oral mucositis for patients with cancer receiving treatment.	2006-04-19	16625538
[18F] fluoromisonidazole and [18F] fluorodeoxyglucose positron emission tomography in response evaluation after chemo-/radiotherapy of non-small-cell lung cancer: a feasibility study.	2006-03-04	16515707
Establishment and characterization of multicellular spheroids from a human glioma cell line; Implications for tumor therapy.	2006-03-02	16509995
Correlation of hypoxic cell fraction and angiogenesis with glucose metabolic rate in gliomas using 18F-fluoromisonidazole, 18F-FDG PET, and immunohistochemical studies.	2006-03	16513609
NanoPET imaging of [(18)F]fluoromisonidazole uptake in experimental mouse tumours.	2006-03	16258762
A meta-analysis of hyperfractionated and accelerated radiotherapy and combined chemotherapy and radiotherapy regimens in unresected locally advanced squamous cell carcinoma of the head and neck.	2006-01-31	16448551
Potentiation of the cytotoxicity of the anticancer agent tirapazamine by benzotriazine N-oxides: the role of redox equilibria.	2006-01-11	16390153
Animal-specific positioning molds for registration of repeat imaging studies: comparative microPET imaging of F18-labeled fluoro-deoxyglucose and fluoro-misonidazole in rodent tumors.	2006-01	16459260
CNS progenitor cells and oligodendrocytes are targets of chemotherapeutic agents in vitro and in vivo.	2006	17125495
Kinetic analysis of dynamic 18F-fluoromisonidazole PET correlates with radiation treatment outcome in head-and-neck cancer.	2005-12-01	16321146
Fully automated synthesis of [18F]fluoromisonidazole using a conventional [18F]FDG module.	2005-11	16253816
Measurement of tumor hypoxia in spontaneous canine sarcomas.	2005-10-19	16229439
Iodinated nitroimidazoles as radiosensitizers.	2005-09-15	16158957
Effects on tumour microcirculation in mice of misonidazole and tumour necrosis factor plus hyperthermia.	1992-01	1733439
Evaluation of a new 2-nitroimidazole nucleoside analogue, RK-28 as a radiosensitizer for clinical use.	1991-01	1671058

Patents

Sample Use Guides

In Vivo Use Guide

Pelvic malignant disease: Oral Misonidazole at a dose of 4 gm/m2 was administered 4-6 hr prior to radiation (total dose 12 g/m2).

Route of Administration: Oral

In Vitro Use Guide

V-79 hamster cells, attached to permanox dishes, were gassed with known concentrations of oxygen (less than 10 to 200,000 ppm) and treated with 1 and 5 mM MISO for 4 h previous to exposure to the chemotherapy agent, melphalan.

Name

Type

Language

Misonidazole

Official Name

English

NSC-261,037

Preferred Name

English

RO 7-0582

Code

English

RO-70582

Code

English

1H-IMIDAZOLE-1-ETHANOL, .ALPHA.-(METHOXYMETHYL)-2-NITRO-

Systematic Name

English

RO-07-0582

Code

English

Misonidazole [WHO-DD]

Common Name

English

NSC-261037

Code

English

?-(Methoxymethyl)-2-nitroimidazole-1-ethanol

Systematic Name

English

MISONIDAZOLE [USAN]

Common Name

English

misonidazole [INN]

Common Name

English

RO 07-0582

Code

English

Misonidazole [MART.]

Common Name

English

RO-7-0582

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C798