Chromium
General Information
Mainterm | Chromium |
CAS Reg.No.(or other ID) | 7440-47-3 |
Regnum |
From www.fda.gov
Computed Descriptors
Download SDF2D Structure | |
CID | 23976 |
IUPAC Name | chromium |
InChI | InChI=1S/Cr |
InChI Key | VYZAMTAEIAYCRO-UHFFFAOYSA-N |
Canonical SMILES | [Cr] |
Molecular Formula | Cr |
From Pubchem
Computed Properties
Property Name | Property Value |
---|---|
Molecular Weight | 51.996 |
Hydrogen Bond Donor Count | 0 |
Hydrogen Bond Acceptor Count | 0 |
Rotatable Bond Count | 0 |
Complexity | 0.0 |
CACTVS Substructure Key Fingerprint | A A A D c Q A A A A A A A A C 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 | 0.0 |
Monoisotopic Mass | 51.941 |
Exact Mass | 51.941 |
Compound Is Canonicalized | True |
Formal Charge | 0 |
Heavy Atom Count | 1 |
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+ | 0.9733 |
Human Intestinal Absorption | HIA+ | 0.9838 |
Caco-2 Permeability | Caco2+ | 0.7354 |
P-glycoprotein Substrate | Non-substrate | 0.8810 |
P-glycoprotein Inhibitor | Non-inhibitor | 0.9787 |
Non-inhibitor | 0.9858 | |
Renal Organic Cation Transporter | Non-inhibitor | 0.9108 |
Distribution | ||
Subcellular localization | Lysosome | 0.5856 |
Metabolism | ||
CYP450 2C9 Substrate | Non-substrate | 0.8466 |
CYP450 2D6 Substrate | Non-substrate | 0.8259 |
CYP450 3A4 Substrate | Non-substrate | 0.8158 |
CYP450 1A2 Inhibitor | Non-inhibitor | 0.8809 |
CYP450 2C9 Inhibitor | Non-inhibitor | 0.9373 |
CYP450 2D6 Inhibitor | Non-inhibitor | 0.9708 |
CYP450 2C19 Inhibitor | Non-inhibitor | 0.9554 |
CYP450 3A4 Inhibitor | Non-inhibitor | 0.9880 |
CYP Inhibitory Promiscuity | Low CYP Inhibitory Promiscuity | 0.8820 |
Excretion | ||
Toxicity | ||
Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.9547 |
Non-inhibitor | 0.9746 | |
AMES Toxicity | Non AMES toxic | 0.9633 |
Carcinogens | Carcinogens | 0.6640 |
Fish Toxicity | Low FHMT | 0.6181 |
Tetrahymena Pyriformis Toxicity | Low TPT | 0.6631 |
Honey Bee Toxicity | High HBT | 0.8315 |
Biodegradation | Ready biodegradable | 0.7326 |
Acute Oral Toxicity | III | 0.5846 |
Carcinogenicity (Three-class) | Warning | 0.4769 |
From admetSAR
ADMET Predicted Profile --- Regression
Model | Value | Unit |
---|---|---|
Absorption | ||
Aqueous solubility | -1.0958 | LogS |
Caco-2 Permeability | 1.6017 | LogPapp, cm/s |
Distribution | ||
Metabolism | ||
Excretion | ||
Toxicity | ||
Rat Acute Toxicity | 2.0135 | LD50, mol/kg |
Fish Toxicity | 1.5413 | pLC50, mg/L |
Tetrahymena Pyriformis Toxicity | -0.7156 | pIGC50, ug/L |
From admetSAR
Toxicity Profile
Route of Exposure | Oral ; inhalation ; dermal |
---|---|
Mechanism of Toxicity | Hexavalent chromium's carcinogenic effects are caused by its metabolites, pentavalent and trivalent chromium. The DNA damage may be caused by hydroxyl radicals produced during reoxidation of pentavalent chromium by hydrogen peroxide molecules present in the cell. Trivalent chromium may also form complexes with peptides, proteins, and DNA, resulting in DNA-protein crosslinks, DNA strand breaks, DNA-DNA interstrand crosslinks, chromium-DNA adducts, chromosomal aberrations and alterations in cellular signaling pathways. It has been shown to induce carcinogenesis by overstimulating cellular regulatory pathways and increasing peroxide levels by activating certain mitogen-activated protein kinases. It can also cause transcriptional repression by cross-linking histone deacetylase 1-DNA methyltransferase 1 complexes to CYP1A1 promoter chromatin, inhibiting histone modification. Chromium may increase its own toxicity by modifying metal regulatory transcription factor 1, causing the inhibition of zinc-induced metallothionein transcription. |
Metabolism | Chromium is absorbed from oral, inhalation, or dermal exposure and distributes to nearly all tissues, with the highest concentrations found in kidney and liver. Bone is also a major storage site and may contribute to long-term retention. Hexavalent chromium's similarity to sulfate and chromate allows it to be transported into cells via sulfate transport mechanisms. Inside the cell, hexavalent chromium is reduced first to pentavalent chromium, then to trivalent chromium by different pathways including ascorbate, glutathione, and nicotinamide adenine dinucleotide. Chromium is almost entirely excreted in the urine. |
Toxicity Values | None |
Lethal Dose | 1 to 3 grams of hexavalent chromium for an adult human. |
Carcinogenicity (IARC Classification) | 3, not classifiable as to its carcinogenicity to humans. |
Minimum Risk Level | Intermediate Oral: 0.005 mg/kg/day (Hexavalent chromium) Chronic Oral: 0.001 mg/kg/day (Hexavalent chromium) |
Health Effects | Hexavalent chromium is a known carcinogen. Chronic inhalation especially has been linked to lung cancer. Hexavalent chromium has also been shown to affect reproduction and development. (A12) |
Treatment | There is no known antidote for chromium poisoning. Exposure is usually handled with symptomatic treatment. |
Reference |
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From T3DB
Taxonomic Classification
Kingdom | Inorganic compounds |
---|---|
Superclass | Homogeneous metal compounds |
Class | Homogeneous transition metal compounds |
Subclass | Not available |
Intermediate Tree Nodes | Not available |
Direct Parent | Homogeneous transition metal compounds |
Alternative Parents |
|
Molecular Framework | Not available |
Substituents | Homogeneous transition metal |
Description | This compound belongs to the class of inorganic compounds known as homogeneous transition metal compounds. These are inorganic compounds containing only metal atoms,with the largest atom being a transition metal atom. |
From ClassyFire
Targets
- General Function:
- Transcription regulatory region sequence-specific dna binding
- Specific Function:
- Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Deacetylates SP proteins, SP1 and SP3, and regulates their function. Component of the BRG1-RB1-HDAC1 complex, which negatively regulates the CREST-mediated transcription in resting neurons. Upon calcium stimulation, HDAC1 is released from the complex and CREBBP is recruited, which facilitates transcriptional activation. Deacetylates TSHZ3 and regulates its transcriptional repressor activity. Deacetylates 'Lys-310' in RELA and thereby inhibits the transcriptional activity of NF-kappa-B. Deacetylates NR1D2 and abrogates the effect of KAT5-mediated relieving of NR1D2 transcription repression activity. Component of a RCOR/GFI/KDM1A/HDAC complex that suppresses, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development. Involved in CIART-mediated transcriptional repression of the circadian transcriptional activator: CLOCK-ARNTL/BMAL1 heterodimer. Required for the transcriptional repression of circadian target genes, such as PER1, mediated by the large PER complex or CRY1 through histone deacetylation.
- Gene Name:
- HDAC1
- Uniprot ID:
- Q13547
- Molecular Weight:
- 55102.615 Da
References
- Schnekenburger M, Talaska G, Puga A: Chromium cross-links histone deacetylase 1-DNA methyltransferase 1 complexes to chromatin, inhibiting histone-remodeling marks critical for transcriptional activation. Mol Cell Biol. 2007 Oct;27(20):7089-101. Epub 2007 Aug 6. [17682057 ]
- General Function:
- Transcriptional activator activity, rna polymerase ii core promoter proximal region sequence-specific binding
- Specific Function:
- Activates the metallothionein I promoter. Binds to the metal responsive element (MRE).
- Gene Name:
- MTF1
- Uniprot ID:
- Q14872
- Molecular Weight:
- 80956.22 Da
References
- Kimura T: [Molecular mechanism involved in chromium(VI) toxicity]. Yakugaku Zasshi. 2007 Dec;127(12):1957-65. [18057785 ]
- General Function:
- Rna polymerase ii carboxy-terminal domain kinase activity
- Specific Function:
- Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade plays also a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are found in the cytosol as well as in other cellular organelles, and those are responsible for processes such as translation, mitosis and apoptosis. Moreover, the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC); as well as in the fragmentation of the Golgi apparatus during mitosis. The substrates include transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of translation (such as EIF4EBP1) and a variety of other signaling-related molecules (like ARHGEF2, DCC, FRS2 or GRB10). Protein kinases (such as RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK, MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are other substrates which enable the propagation the MAPK/ERK signal to additional cytosolic and nuclear targets, thereby extending the specificity of the cascade. Mediates phosphorylation of TPR in respons to EGF stimulation. May play a role in the spindle assembly checkpoint. Phosphorylates PML and promotes its interaction with PIN1, leading to PML degradation.Acts as a transcriptional repressor. Binds to a [GC]AAA[GC] consensus sequence. Repress the expression of interferon gamma-induced genes. Seems to bind to the promoter of CCL5, DMP1, IFIH1, IFITM1, IRF7, IRF9, LAMP3, OAS1, OAS2, OAS3 and STAT1. Transcriptional activity is independent of kinase activity.
- Gene Name:
- MAPK1
- Uniprot ID:
- P28482
- Molecular Weight:
- 41389.265 Da
References
- Kim G, Yurkow EJ: Chromium induces a persistent activation of mitogen-activated protein kinases by a redox-sensitive mechanism in H4 rat hepatoma cells. Cancer Res. 1996 May 1;56(9):2045-51. [8616849 ]
- General Function:
- Phosphatase binding
- Specific Function:
- Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade plays also a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are found in the cytosol as well as in other cellular organelles, and those are responsible for processes such as translation, mitosis and apoptosis. Moreover, the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC); as well as in the fragmentation of the Golgi apparatus during mitosis. The substrates include transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of translation (such as EIF4EBP1) and a variety of other signaling-related molecules (like ARHGEF2, FRS2 or GRB10). Protein kinases (such as RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK, MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are other substrates which enable the propagation the MAPK/ERK signal to additional cytosolic and nuclear targets, thereby extending the specificity of the cascade.
- Gene Name:
- MAPK3
- Uniprot ID:
- P27361
- Molecular Weight:
- 43135.16 Da
References
- Kim G, Yurkow EJ: Chromium induces a persistent activation of mitogen-activated protein kinases by a redox-sensitive mechanism in H4 rat hepatoma cells. Cancer Res. 1996 May 1;56(9):2045-51. [8616849 ]
- General Function:
- Transferrin receptor binding
- Specific Function:
- Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites of absorption and heme degradation to those of storage and utilization. Serum transferrin may also have a further role in stimulating cell proliferation.
- Gene Name:
- TF
- Uniprot ID:
- P02787
- Molecular Weight:
- 77063.195 Da
References
- Moshtaghie AA, Ani M, Bazrafshan MR: Comparative binding study of aluminum and chromium to human transferrin. Effect of iron. Biol Trace Elem Res. 1992 Jan-Mar;32:39-46. [1375080 ]
- General Function:
- Metal ion binding
- Specific Function:
- Cytochrome b5 is a membrane bound hemoprotein which function as an electron carrier for several membrane bound oxygenases.
- Gene Name:
- CYB5A
- Uniprot ID:
- P00167
- Molecular Weight:
- 15329.985 Da
From T3DB