MANGANOUS OXIDE

General Information

Mainterm	MANGANOUS OXIDE
Doc Type	NUL
CAS Reg.No.(or other ID)	1344-43-0
Regnum	582.80

From www.fda.gov

Computed Descriptors

Download SDF

2D Structure
CID	14940
IUPAC Name	oxomanganese
InChI	InChI=1S/Mn.O
InChI Key	VASIZKWUTCETSD-UHFFFAOYSA-N
Canonical SMILES	O=[Mn]
Molecular Formula	MnO
Wikipedia	manganese(II) oxide

From Pubchem

Computed Properties

Property Name	Property Value
Molecular Weight	70.937
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	1
Rotatable Bond Count	0
Complexity	2.0
CACTVS Substructure Key Fingerprint	A A A D c Q A A I A A A A A B A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A = =
Topological Polar Surface Area	17.1
Monoisotopic Mass	70.933
Exact Mass	70.933
Compound Is Canonicalized	True
Formal Charge	0
Heavy Atom Count	2
Defined Atom Stereocenter Count	0
Undefined Atom Stereocenter Count	0
Defined Bond Stereocenter Count	0
Undefined Bond Stereocenter Count	0
Isotope Atom Count	0
Covalently-Bonded Unit Count	1

From Pubchem

ADMET Predicted Profile --- Classification

Model	Result	Probability
Absorption
Blood-Brain Barrier	BBB+	0.9837
Human Intestinal Absorption	HIA+	0.9838
Caco-2 Permeability	Caco2+	0.6708
P-glycoprotein Substrate	Non-substrate	0.8922
P-glycoprotein Inhibitor	Non-inhibitor	0.9725
P-glycoprotein Inhibitor	Non-inhibitor	0.9950
Renal Organic Cation Transporter	Non-inhibitor	0.9248
Distribution
Subcellular localization	Lysosome	0.4909
Metabolism
CYP450 2C9 Substrate	Non-substrate	0.8638
CYP450 2D6 Substrate	Non-substrate	0.8940
CYP450 3A4 Substrate	Non-substrate	0.8026
CYP450 1A2 Inhibitor	Non-inhibitor	0.8153
CYP450 2C9 Inhibitor	Non-inhibitor	0.9267
CYP450 2D6 Inhibitor	Non-inhibitor	0.9535
CYP450 2C19 Inhibitor	Non-inhibitor	0.9338
CYP450 3A4 Inhibitor	Non-inhibitor	0.9869
CYP Inhibitory Promiscuity	Low CYP Inhibitory Promiscuity	0.9062
Excretion
Toxicity
Human Ether-a-go-go-Related Gene Inhibition	Weak inhibitor	0.9031
Human Ether-a-go-go-Related Gene Inhibition	Non-inhibitor	0.9770
AMES Toxicity	Non AMES toxic	0.7478
Carcinogens	Carcinogens	0.7198
Fish Toxicity	Low FHMT	0.8052
Tetrahymena Pyriformis Toxicity	Low TPT	0.6348
Honey Bee Toxicity	High HBT	0.8162
Biodegradation	Ready biodegradable	0.7705
Acute Oral Toxicity	II	0.5839
Carcinogenicity (Three-class)	Non-required	0.5245

From admetSAR

ADMET Predicted Profile --- Regression

Model	Value	Unit
Absorption
Aqueous solubility	-0.1974	LogS
Caco-2 Permeability	1.4111	LogPapp, cm/s
Distribution
Metabolism
Excretion
Toxicity
Rat Acute Toxicity	2.2618	LD50, mol/kg
Fish Toxicity	1.6549	pLC50, mg/L
Tetrahymena Pyriformis Toxicity	-0.8438	pIGC50, ug/L

From admetSAR

Toxicity Profile

Route of Exposure	Oral ; inhalation
Mechanism of Toxicity	Manganese 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.
Metabolism	Manganese is absorbed mainly via ingestion, but can also be inhaled. It binds to alpha-2-macroglobulin, albumin, or transferrin in the plasma and is distributed to the brain and all other mammalian tissues, though it tends to accumulate more in the liver, pancreas, and kidney. Manganese is capable of existing in a number of oxidation states and is believed to undergo changes in oxidation state within the body. Manganese oxidation state can influence tissue toxicokinetic behavior, and possibly toxicity. Manganese is excreted primarily in the faeces.
Toxicity Values	None
Lethal Dose	None
Carcinogenicity (IARC Classification)	No indication of carcinogenicity to humans (not listed by IARC).
Minimum Risk Level	Chronic Inhalation: 0.0003 mg/m3
Health Effects	Manganese 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”. (L228)
Treatment	EYES: irrigate opened eyes for several minutes under running water. INGESTION: do not induce vomiting. Rinse mouth with water (never give anything by mouth to an unconscious person). Seek immediate medical advice. SKIN: should be treated immediately by rinsing the affected parts in cold running water for at least 15 minutes, followed by thorough washing with soap and water. If necessary, the person should shower and change contaminated clothing and shoes, and then must seek medical attention. INHALATION: supply fresh air. If required provide artificial respiration.
Reference

From T3DB

Taxonomic Classification

Kingdom	Inorganic compounds
Superclass	Mixed metal/non-metal compounds
Class	Transition metal organides
Subclass	Transition metal oxides
Intermediate Tree Nodes	Not available
Direct Parent	Transition metal oxides
Alternative Parents	Inorganic salts Inorganic oxides
Molecular Framework	Not available
Substituents	Transition metal oxide - Inorganic oxide - Inorganic salt
Description	This compound belongs to the class of inorganic compounds known as transition metal oxides. These are inorganic compounds containing an oxygen atom of an oxidation state of -2, in which the heaviest atom bonded to the oxygen is a transition metal.

From ClassyFire

Targets

Target Details

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

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

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

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

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

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

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

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

Putative testis-specific prion protein

Gene Name:: PRNT
Uniprot ID:: Q86SH4
Molecular Weight:: 10755.655 Da

References

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 ]

From T3DB