Details
| Stereochemistry | RACEMIC |
| Molecular Formula | C11H18N4O3 |
| Molecular Weight | 254.2856 |
| Optical Activity | ( + / - ) |
| Defined Stereocenters | 0 / 1 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
OC(CN1C=CN=C1[N+]([O-])=O)CN2CCCCC2
InChI
InChIKey=WVWOOAYQYLJEFD-UHFFFAOYSA-N
InChI=1S/C11H18N4O3/c16-10(8-13-5-2-1-3-6-13)9-14-7-4-12-11(14)15(17)18/h4,7,10,16H,1-3,5-6,8-9H2
| Molecular Formula | C11H18N4O3 |
| Molecular Weight | 254.2856 |
| Charge | 0 |
| Count |
|
| Stereochemistry | RACEMIC |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 1 |
| E/Z Centers | 0 |
| Optical Activity | ( + / - ) |
Pimonidazole (developed as RO 038799) is a derivative of 2-nitroimidazole, which forms adducts (binds to thiol-containing proteins) only at low oxygen tension. Pimonidazole is a novel nontoxic hypoxia marker for the complementary study of tumor hypoxia and cell proliferation in different types of cancer. The drawback of pimonidazole as a hypoxic marker is that it detects only severe hypoxia.
Originator
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: thiol-containing proteins specifically in hypoxic cells Sources: https://www.ncbi.nlm.nih.gov/pubmed/9826471 |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Diagnostic | Unknown Approved UseUnknown |
|||
| Diagnostic | Unknown Approved UseUnknown |
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| Diagnostic | Unknown Approved UseUnknown |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
4.01 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6519157 |
87 mg single, intravenous dose: 87 mg route of administration: Intravenous experiment type: SINGLE co-administered: |
PIMONIDAZOLE plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
27.925 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6519157 |
460 mg single, intravenous dose: 460 mg route of administration: Intravenous experiment type: SINGLE co-administered: |
PIMONIDAZOLE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Inhibition of mitochondrial respiration elevates oxygen concentration but leaves regulation of hypoxia-inducible factor (HIF) intact. | 2005-10-01 |
|
| Comparison of different methods of CAIX quantification in relation to hypoxia in three human head and neck tumor lines. | 2005-08 |
|
| Ischemia-induced cleavage of cadherins in NRK cells: evidence for a role of metalloproteinases. | 2005-08 |
|
| Correction of anaemia through the use of darbepoetin alfa improves chemotherapeutic outcome in a murine model of Lewis lung carcinoma. | 2005-07-25 |
|
| Hypoxic cell turnover in different solid tumor lines. | 2005-07-15 |
|
| Observation of incipient tumor angiogenesis that is independent of hypoxia and hypoxia inducible factor-1 activation. | 2005-07-01 |
|
| Tirapazamine administered as a neoadjuvant to radiotherapy reduces metastatic dissemination. | 2005-06-01 |
|
| Dependence of FDG uptake on tumor microenvironment. | 2005-06-01 |
|
| Role of the hypoxic bone marrow microenvironment in 5T2MM murine myeloma tumor progression. | 2005-06 |
|
| Hypoxia-regulated glucose transporter Glut-1 may influence chemosensitivity to some alkylating agents: results of EORTC (First Translational Award) study of the relevance of tumour hypoxia to the outcome of chemotherapy in human tumour-derived xenografts. | 2005-06 |
|
| A kinetic model for dynamic [18F]-Fmiso PET data to analyse tumour hypoxia. | 2005-05-21 |
|
| Interleukin-12 has no effect on vascular density, perfusion, hypoxia and proliferation of an implanted human squamous cell carcinoma xenograft tumour despite up-regulation of ICAM-1. | 2005-05-05 |
|
| Assessment of regional tumor hypoxia using 18F-fluoromisonidazole and 64Cu(II)-diacetyl-bis(N4-methylthiosemicarbazone) positron emission tomography: Comparative study featuring microPET imaging, Po2 probe measurement, autoradiography, and fluorescent microscopy in the R3327-AT and FaDu rat tumor models. | 2005-04-01 |
|
| The tumor bed effect: increased metastatic dissemination from hypoxia-induced up-regulation of metastasis-promoting gene products. | 2005-03-15 |
|
| Real-time imaging of hypoxia-inducible factor-1 activity in tumor xenografts. | 2005-03 |
|
| Phenytoin teratogenicity: hypoxia marker and effects on embryonic heart rhythm suggest an hERG-related mechanism. | 2005-03 |
|
| Expression of the proapoptotic protein Bid is an adverse prognostic factor for radiotherapy outcome in carcinoma of the cervix. | 2005-02-14 |
|
| Inhibition of tumor necrosis factor-alpha improves physiological angiogenesis and reduces pathological neovascularization in ischemic retinopathy. | 2005-02 |
|
| Up-regulation of HIF in experimental acute renal failure: evidence for a protective transcriptional response to hypoxia. | 2005-02 |
|
| Erythropoietin and erythropoietin receptor expression in head and neck cancer: relationship to tumor hypoxia. | 2005-01-01 |
|
| Mechanism of hypertensive nephropathy in the Dahl/Rapp rat: a primary disorder of vascular smooth muscle. | 2005-01 |
|
| Hypoxia-inducible factor 1alpha expression as an intrinsic marker of hypoxia: correlation with tumor oxygen, pimonidazole measurements, and outcome in locally advanced carcinoma of the cervix. | 2004-12-15 |
|
| Lack of microvessels in well-differentiated regions of human head and neck squamous cell carcinoma A253 associated with functional magnetic resonance imaging detectable hypoxia, limited drug delivery, and resistance to irinotecan therapy. | 2004-12-01 |
|
| Evaluation of hypoxia in an experimental rat tumour model by [(18)F]fluoromisonidazole PET and immunohistochemistry. | 2004-11-29 |
|
| Identification of differentially expressed genes in a renal cell carcinoma tumor model after endostatin-treatment. | 2004-11 |
|
| Microregional effects of gemcitabine in HCT-116 xenografts. | 2004-09-15 |
|
| Quantifying transient hypoxia in human tumor xenografts by flow cytometry. | 2004-09-01 |
|
| Tumor-dependent kinetics of partial pressure of oxygen fluctuations during air and oxygen breathing. | 2004-09-01 |
|
| Effects of nicotinamide and carbogen in different murine colon carcinomas: immunohistochemical analysis of vascular architecture and microenvironmental parameters. | 2004-09-01 |
|
| The immunohistochemical assessment of hypoxia, vascularity and proliferation in bladder carcinoma. | 2004-08 |
|
| Tumor hypoxia correlates with metastatic tumor growth of pancreatic cancer in an orthotopic murine model. | 2004-08 |
|
| Overexpression of dimethylarginine dimethylaminohydrolase enhances tumor hypoxia: an insight into the relationship of hypoxia and angiogenesis in vivo. | 2004-07-17 |
|
| In vivo evaluation of [18F]fluoroetanidazole as a new marker for imaging tumour hypoxia with positron emission tomography. | 2004-06-01 |
|
| Hypoperfusion of peritubular capillaries induces chronic hypoxia before progression of tubulointerstitial injury in a progressive model of rat glomerulonephritis. | 2004-06 |
|
| Improved immunohistochemical method for detecting hypoxia gradients in mouse tissues and tumors. | 2004-06 |
|
| Evidence of tubular hypoxia in the early phase in the remnant kidney model. | 2004-05 |
|
| TNP-470 promotes initial vascular sprouting in xenograft tumors. | 2004-03 |
|
| Evidence that involucrin, a marker for differentiation, is oxygen regulated in human squamous cell carcinomas. | 2004-02-09 |
|
| Neuroblastoma survival and death: an in vitro model of hypoxia and metabolic stress. | 2004-02 |
|
| Expression of the pro-angiogenic factors vascular endothelial growth factor and interleukin-8/CXCL8 by human breast carcinomas is responsive to nutrient deprivation and endoplasmic reticulum stress. | 2004-01-22 |
|
| Increased metastatic dissemination in human melanoma xenografts after subcurative radiation treatment: radiation-induced increase in fraction of hypoxic cells and hypoxia-induced up-regulation of urokinase-type plasminogen activator receptor. | 2004-01-01 |
|
| Differentiation-associated staining with anti-pimonidazole antibodies in head and neck tumors. | 2004-01 |
|
| Analysis of the regional uptake of radiolabeled deoxyglucose analogs in human tumor xenografts. | 2004-01 |
|
| Teratogenicity by the hERG potassium channel blocking drug almokalant: use of hypoxia marker gives evidence for a hypoxia-related mechanism mediated via embryonic arrhythmia. | 2003-12-01 |
|
| Endogenous markers of tumor hypoxia predictors of clinical radiation resistance? | 2003-12 |
|
| The effect of elevated intraocular oxygen on organelle degradation in the embryonic chicken lens. | 2003-12 |
|
| Hypoxia and differentiation in squamous cell carcinomas of the uterine cervix: pimonidazole and involucrin. | 2003-10-15 |
|
| GLUT1 and CAIX as intrinsic markers of hypoxia in bladder cancer: relationship with vascularity and proliferation as predictors of outcome of ARCON. | 2003-10-06 |
|
| Tumor oxygen dynamics: correlation of in vivo MRI with histological findings. | 2003-09-27 |
|
| Proliferation and micromilieu during fractionated irradiation of human FaDu squamous cell carcinoma in nude mice. | 2003-07 |
Patents
Sample Use Guides
Ten patients with cervical carcinoma received 0.5 g/m2 pimonidazole intravenously followed by biopsy of the cervical carcinoma the next day. Hypoxic cells were recognized by immunohistochemical detection of pimonidazole using a mouse monoclonal antibody.
(18)F-Fluoroazomycin arabinoside (FAZA) will be administered via intravenous injection at a dose of 5.2 MBq/kg with a minimum dose of 100 MBq (2.7 mCi) and a maximum dose of 600 MBq (16.2 mCi) prior to positron emission tomography (PET) imaging. A single dose of oral pimonidazole capsules at a dose of 0.5 g/m2, will be taken by participants 16-20 hours prior to tumor resection surgery.
Route of Administration:
Other
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/21296882
The high demand of mitochondrial respiration during insulin secretion, pancreatic β-cells consume large amounts of oxygen in a short time period. There was examined the effect of insulin secretion on cellular oxygen tension in vitro. It was confirmed that Western blotting of pimonidazole adduct was more sensitive than immunostaining for detection of cellular hypoxia in vitro. In MIN6 cells, a pancreatic β-cell line, pimonidazole adduct formation, and stabilization of hypoxia-inducible factor-1α (HIF-1α) were detected under mildly hypoxic conditions. MIN6 cells and PANC-1 cells were incubated at various oxygen tensions in the presence of pimonidazole (10 μM) for 3 h.
| Substance Class |
Chemical
Created
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Edited
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| Record UNII |
46JO4D76R2
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| Record Status |
Validated (UNII)
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C798
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ENANTIOMER -> RACEMATE |
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ACTIVE MOIETY |