Mangafodipir (T3D1137)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (5)XML
Targets (5)
Record Information
Version2.0
Creation Date2009-06-19 21:58:21 UTC
Update Date2014-12-24 20:23:12 UTC
Accession NumberT3D1137
Identification
Common NameMangafodipir
ClassSmall Molecule
DescriptionMangafodipir is a contrast agent delivered intravenously to enhance contrast in magnetic resonance imaging (MRI) of the liver. It has two parts, paramagnetic manganese (II) ions and the chelating agent fodipir (dipyridoxyl diphosphate, DPDP). Normal liver tissue absorbs the manganese more than abnormal or cancerous tissue. The manganese shortens the longitudinal relaxation time (called T1), making the normal tissue appear brighter in MRIs. This enhanced contrast allows lesions to be more easily identified. Acute toxicity studies in mice, rats and dogs using IV administration showed mangafodipir to have low to moderate toxicity. Repeat dose toxicity studies were conducted in rats, cynomologous monkeys and dogs. The liver and to a lesser extent the kidney were target organs of toxicity.
Compound Type
  • Amine
  • Industrial/Workplace Toxin
  • Manganese Compound
  • Organic Compound
  • Organometallic
  • Pollutant
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
Mangafodipir trisodium
Teslascan
Chemical FormulaC22H27MnN4Na3O14P2
Average Molecular Mass757.323 g/mol
Monoisotopic Mass757.007 g/mol
CAS Registry Number140678-14-4
IUPAC Namemanganese(2+) ion trisodium 2-({2-[(carboxylatomethyl)({5-[(hydrogen phosphonatooxy)methyl]-2-methyl-3-oxidopyridin-4-yl}methyl)amino]ethyl}({2-methyl-3-oxido-5-[(phosphonooxy)methyl]pyridin-4-yl}methyl)amino)acetate
Traditional Namemanganese(2+) ion trisodium 2-({2-[(carboxylatomethyl)({5-[(hydrogen phosphonatooxy)methyl]-2-methyl-3-oxidopyridin-4-yl}methyl)amino]ethyl}({2-methyl-3-oxido-5-[(phosphonooxy)methyl]pyridin-4-yl}methyl)amino)acetate
SMILES[Na+].[Na+].[Na+].[Mn++].CC1=C([O-])C(CN(CCN(CC([O-])=O)CC2=C(COP(O)([O-])=O)C=NC(C)=C2[O-])CC([O-])=O)=C(COP(O)(O)=O)C=N1
InChI IdentifierInChI=1S/C22H32N4O14P2.Mn.3Na/c1-13-21(31)17(15(5-23-13)11-39-41(33,34)35)7-25(9-19(27)28)3-4-26(10-20(29)30)8-18-16(12-40-42(36,37)38)6-24-14(2)22(18)32;;;;/h5-6,31-32H,3-4,7-12H2,1-2H3,(H,27,28)(H,29,30)(H2,33,34,35)(H2,36,37,38);;;;/q;+2;3*+1/p-5
InChI KeyInChIKey=BENFPBJLMUIGGD-UHFFFAOYSA-I
Chemical Taxonomy
Description belongs to the class of organic compounds known as pyridoxamine 5'-phosphates. These are heterocyclic aromatic compounds containing a pyridoxamine that carries a phosphate group at the 5'-position.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassPyridines and derivatives
Sub ClassPyridoxamines
Direct ParentPyridoxamine 5'-phosphates
Alternative Parents
Substituents
  • Pyridoxamine 5'-phosphate
  • Alpha-amino acid
  • Alpha-amino acid or derivatives
  • Pyridinolate
  • Aralkylamine
  • Methylpyridine
  • Phosphoric acid ester
  • Alkyl phosphate
  • Organic phosphoric acid derivative
  • Dicarboxylic acid or derivatives
  • Heteroaromatic compound
  • Amino acid or derivatives
  • Tertiary amine
  • Tertiary aliphatic amine
  • Carboxylic acid salt
  • Amino acid
  • Azacycle
  • Organic alkali metal salt
  • Organic transition metal salt
  • Carboxylic acid
  • Carboxylic acid derivative
  • Organic nitrogen compound
  • Organooxygen compound
  • Organonitrogen compound
  • Organic zwitterion
  • Organic salt
  • Organic sodium salt
  • Hydrocarbon derivative
  • Organic oxide
  • Carbonyl group
  • Organopnictogen compound
  • Amine
  • Organic oxygen compound
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External DescriptorsNot Available
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Mitochondrion
Biofluid LocationsNot Available
Tissue LocationsNot Available
Pathways
NameSMPDB LinkKEGG Link
ApoptosisNot Availablemap04210
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateLiquid
AppearanceLiquid
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
SolubilityNot Available
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility8.43 g/LALOGPS
logP0.88ALOGPS
logP-1.9ChemAxon
logS-2ALOGPS
pKa (Strongest Acidic)1.44ChemAxon
pKa (Strongest Basic)-6.4ChemAxon
Physiological Charge-5ChemAxon
Hydrogen Acceptor Count16ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area294.99 ŲChemAxon
Rotatable Bond Count17ChemAxon
Refractivity185.26 m³·mol⁻¹ChemAxon
Polarizability55.1 ųChemAxon
Number of Rings2ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0a4i-0000000900-90d667d5611bc91eb5d82019-02-23View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0a4i-0000000900-90d667d5611bc91eb5d82019-02-23View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0a4i-0000000900-90d667d5611bc91eb5d82019-02-23View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0a4i-0000000900-52c507de86c5c97a522a2019-02-23View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0a4i-0000000900-52c507de86c5c97a522a2019-02-23View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a4i-0000000900-52c507de86c5c97a522a2019-02-23View Spectrum
Toxicity Profile
Route of ExposureOral (3) ; inhalation (3)
Mechanism of ToxicityManganese is a cellular toxicant that can impair transport systems, enzyme activities, and receptor functions. It primarily targets the central nervous system, particularily the globus pallidus of the basal ganglia. It is believed that the manganese ion, Mn(II), enhances the autoxidation or turnover of various intracellular catecholamines, leading to increased production of free radicals, reactive oxygen species, and other cytotoxic metabolites, along with a depletion of cellular antioxidant defense mechanisms, leading to oxidative damage and selective destruction of dopaminergic neurons. In addition to dopamine, manganese is thought to perturbations other neurotransmitters, such as GABA and glutamate. In order to produce oxidative damage, manganese must first overwhelm the antioxidant enzyme manganese superoxide dismutase. The neurotoxicity of Mn(II) has also been linked to its ability to substitute for Ca(II) under physiological conditions. It can enter mitochondria via the calcium uniporter and inhibit mitochondrial oxidative phosphorylation. It may also inhibit the efflux of Ca(II), which can result in a loss of mitochondrial membrane integrity. Mn(II) has been shown to inhibit mitochondrial aconitase activity to a significant level, altering amino acid metabolism and cellular iron homeostasis. (3)
MetabolismMetabolism of organophosphates occurs principally by oxidation, by hydrolysis via esterases and by reaction with glutathione. Demethylation and glucuronidation may also occur. Oxidation of organophosphorus pesticides may result in moderately toxic products. In general, phosphorothioates are not directly toxic but require oxidative metabolism to the proximal toxin. The glutathione transferase reactions produce products that are, in most cases, of low toxicity. Paraoxonase (PON1) is a key enzyme in the metabolism of organophosphates. PON1 can inactivate some organophosphates through hydrolysis. PON1 hydrolyzes the active metabolites in several organophosphates insecticides as well as, nerve agents such as soman, sarin, and VX. The presence of PON1 polymorphisms causes there to be different enzyme levels and catalytic efficiency of this esterase, which in turn suggests that different individuals may be more susceptible to the toxic effect of organophosphate exposure.
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesMangafodipir is a contrast agent delivered intravenously to enhance contrast in magnetic resonance imaging (MRI) of the liver. (5)
Minimum Risk LevelChronic Inhalation: 0.0003 mg/m3 (2)
Health EffectsManganese mainly affects the nervous system and may cause behavioral changes and other nervous system effects, which include movements that may become slow and clumsy. This combination of symptoms when sufficiently severe is referred to as “manganism”. (3)
SymptomsManganese mainly affects the nervous system and may cause behavioral changes and other nervous system effects, which include movements that may become slow and clumsy. This combination of symptoms when sufficiently severe is referred to as “manganism”. (3)
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDNot Available
PubChem Compound ID160036
ChEMBL IDNot Available
ChemSpider ID140690
KEGG IDNot Available
UniProt IDNot Available
OMIM ID
ChEBI IDNot Available
BioCyc IDNot Available
CTD IDNot Available
Stitch IDMangafodipir
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkNot Available
References
Synthesis ReferenceNot Available
MSDST3D1137.pdf
General References
  1. Klaassen C and Watkins J (2003). Casarett and Doull's Essentials of Toxicology. New York, NY: McGraw-Hill.
  2. ATSDR - Agency for Toxic Substances and Disease Registry (2001). Minimal Risk Levels (MRLs) for Hazardous Substances. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
  3. ATSDR - Agency for Toxic Substances and Disease Registry (2008). Toxicological profile for manganese. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
  4. Wikipedia. Manganese. Last Updated 26 May 2009. [Link]
  5. Wikipedia. Mangafodipir . Last Updated 8 August 2008. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. Aconitate hydratase, mitochondrial
General Function:
Iron ion binding
Specific Function:
Catalyzes the isomerization of citrate to isocitrate via cis-aconitate.
Gene Name:
ACO2
Uniprot ID:
Q99798
Molecular Weight:
85424.745 Da
References
  1. Crooks DR, Ghosh MC, Braun-Sommargren M, Rouault TA, Smith DR: Manganese targets m-aconitase and activates iron regulatory protein 2 in AF5 GABAergic cells. J Neurosci Res. 2007 Jun;85(8):1797-809. [17469137 ]
Target Details
2. Cytoplasmic aconitate hydratase
General Function:
Rna binding
Specific Function:
Iron sensor. Binds a 4Fe-4S cluster and functions as aconitase when cellular iron levels are high. Functions as mRNA binding protein that regulates uptake, sequestration and utilization of iron when cellular iron levels are low. Binds to iron-responsive elements (IRES) in target mRNA species when iron levels are low. Binding of a 4Fe-4S cluster precludes RNA binding.Catalyzes the isomerization of citrate to isocitrate via cis-aconitate.
Gene Name:
ACO1
Uniprot ID:
P21399
Molecular Weight:
98398.14 Da
References
  1. Crooks DR, Ghosh MC, Braun-Sommargren M, Rouault TA, Smith DR: Manganese targets m-aconitase and activates iron regulatory protein 2 in AF5 GABAergic cells. J Neurosci Res. 2007 Jun;85(8):1797-809. [17469137 ]
Target Details
3. Iron-responsive element-binding protein 2
General Function:
Translation repressor activity
Specific Function:
RNA-binding protein that binds to iron-responsive elements (IRES), which are stem-loop structures found in the 5'-UTR of ferritin, and delta aminolevulinic acid synthase mRNAs, and in the 3'-UTR of transferrin receptor mRNA. Binding to the IRE element in ferritin results in the repression of its mRNA translation. Binding of the protein to the transferrin receptor mRNA inhibits the degradation of this otherwise rapidly degraded mRNA.
Gene Name:
IREB2
Uniprot ID:
P48200
Molecular Weight:
105043.65 Da
References
  1. Crooks DR, Ghosh MC, Braun-Sommargren M, Rouault TA, Smith DR: Manganese targets m-aconitase and activates iron regulatory protein 2 in AF5 GABAergic cells. J Neurosci Res. 2007 Jun;85(8):1797-809. [17469137 ]
Target Details
4. Major prion protein
General Function:
Tubulin binding
Specific Function:
Its primary physiological function is unclear. Has cytoprotective activity against internal or environmental stresses. May play a role in neuronal development and synaptic plasticity. May be required for neuronal myelin sheath maintenance. May play a role in iron uptake and iron homeostasis. Soluble oligomers are toxic to cultured neuroblastoma cells and induce apoptosis (in vitro) (PubMed:12732622, PubMed:19936054, PubMed:20564047). Association with GPC1 (via its heparan sulfate chains) targets PRNP to lipid rafts. Also provides Cu(2+) or ZN(2+) for the ascorbate-mediated GPC1 deaminase degradation of its heparan sulfate side chains (By similarity).
Gene Name:
PRNP
Uniprot ID:
P04156
Molecular Weight:
27661.21 Da
References
  1. Brazier MW, Davies P, Player E, Marken F, Viles JH, Brown DR: Manganese binding to the prion protein. J Biol Chem. 2008 May 9;283(19):12831-9. doi: 10.1074/jbc.M709820200. Epub 2008 Mar 10. [18332141 ]
Target Details
5. Putative testis-specific prion protein
General Function:
Not Available
Specific Function:
Not Available
Gene Name:
PRNT
Uniprot ID:
Q86SH4
Molecular Weight:
10755.655 Da
References
  1. Brazier MW, Davies P, Player E, Marken F, Viles JH, Brown DR: Manganese binding to the prion protein. J Biol Chem. 2008 May 9;283(19):12831-9. doi: 10.1074/jbc.M709820200. Epub 2008 Mar 10. [18332141 ]