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Tetrathiomolybdate

PubChem CID
5245480
Structure
Tetrathiomolybdate_small.png
Molecular Formula
Synonyms
  • Tetrathiomolybdate
  • Thiomolybdate
  • 16330-92-0
  • Tiomolibdate ion
  • Tetrathioxomolybdate(2-)
Molecular Weight
226.2 g/mol
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Dates
  • Create:
    2004-09-16
  • Modify:
    2025-01-18
Description
Tetrathiomolybdate(2-) is a molybdenum coordination entity. It has a role as a copper chelator.
Tetrathiomolybdate is an oral, small-molecule, anticopper agent that is highly specific for lowering the levels of free copper in serum. COPREXA has completed pivotal clinical trials for the treatment of neurologic Wilson's disease. It is also developed for fibrotic disorders based upon the rationale that the fibrotic disease process is dependent upon the availability of free copper in the body.
Tetrathiomolybdate is an orally bioavailable metal copper (Cu) chelator, with potential antiangiogenic, anti-metastatic and antitumor activities. Upon oral administration, tetrathiomolybdate (TM) targets and binds to copper and food protein in the gastrointestinal (GI) tract, thereby forming stable complexes and preventing copper uptake and reabsorption. Additionally, absorbed free TM targets and binds to copper and serum albumin in the bloodstream. This depletes systemic copper reserves and deprives the tumor microenvironment (TME) from copper. Chelation of copper by TM downregulates the expression of angiogenic factors of which copper is a cofactor, such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), and prevents the production of nuclear factor-kappa B (NF-kB). Copper deprivation also inhibits the activity and levels of copper-dependent angiogenic enzymes, such as vascular endothelial growth factor receptor (VEGFR). This modulates the activity of VEGFR-positive endothelial progenitor cells (EPCs) that are necessary for metastasis. EPC deficiency results in the inhibition of angiogenesis and prevents metastasis. TM also inhibits the activities of other copper-containing metalloenzymes, including superoxide dismutase 1 (SOD1) in endothelial cells, cytochrome C oxidase, vascular adhesion protein-1 (VAP-1), antioxidant 1 copper chaperone (ATOX-1) and matrix metalloproteinase 9 (MMP-9). Inhibition of these enzymes interferes with the activation of several signal transduction pathways required for cellular proliferation and angiogenesis. TM also inhibits the activity and levels of lysyl oxidase-like 2 (LOXL2; lysyl oxidase homolog 2), a copper dependent amine oxidase that is critical for modeling the pre-metastatic niche and promotes metastasis, tumor cell migration and invasiveness. In addition, copper depletion also attenuates the activation of host cells within the tumor microenvironment including cancer-associated fibroblasts (CAFs), modulates tumor associated macrophages (TAMs) and promotes cytotoxic T-lymphocyte (CTL)-mediated anti-tumor immune responses.

1 Structures

1.1 2D Structure

Chemical Structure Depiction
Tetrathiomolybdate.png

1.2 3D Status

Conformer generation is disallowed since MMFF94s unsupported element, mixture or salt

2 Names and Identifiers

2.1 Computed Descriptors

2.1.1 IUPAC Name

bis(sulfanylidene)molybdenum;sulfanide
Computed by Lexichem TK 2.7.0 (PubChem release 2021.10.14)

2.1.2 InChI

InChI=1S/Mo.2H2S.2S/h;2*1H2;;/p-2
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.3 InChIKey

VVRHUOPINLMZBL-UHFFFAOYSA-L
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.4 SMILES

[SH-].[SH-].S=[Mo]=S
Computed by OEChem 2.3.0 (PubChem release 2024.12.12)

2.2 Molecular Formula

H2MoS4-2
Computed by PubChem 2.2 (PubChem release 2021.10.14)

2.3 Other Identifiers

2.3.1 CAS

16330-92-0

2.3.3 European Community (EC) Number

2.3.4 UNII

2.3.5 ChEBI ID

2.3.6 DrugBank ID

2.3.7 NCI Thesaurus Code

2.3.8 Wikidata

2.4 Synonyms

2.4.1 MeSH Entry Terms

  • ammonium tetrathiomolybdate
  • ATN-224
  • tetrathiomolybdate
  • tetrathiomolybdate bis-choline salt
  • tetrathiomolybdate, dipotassium salt
  • tetrathiomolybdate, disodium salt
  • thiomolybdate
  • TTM cpd

2.4.2 Depositor-Supplied Synonyms

3 Chemical and Physical Properties

3.1 Computed Properties

Property Name
Molecular Weight
Property Value
226.2 g/mol
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Donor Count
Property Value
2
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Acceptor Count
Property Value
4
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Rotatable Bond Count
Property Value
0
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Exact Mass
Property Value
227.809338 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Monoisotopic Mass
Property Value
227.809338 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Topological Polar Surface Area
Property Value
66.2 Ų
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Heavy Atom Count
Property Value
5
Reference
Computed by PubChem
Property Name
Formal Charge
Property Value
-2
Reference
Computed by PubChem
Property Name
Complexity
Property Value
19.1
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Isotope Atom Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Atom Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Undefined Atom Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Undefined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Covalently-Bonded Unit Count
Property Value
3
Reference
Computed by PubChem
Property Name
Compound Is Canonicalized
Property Value
Yes
Reference
Computed by PubChem (release 2021.10.14)

3.2 Experimental Properties

3.2.1 Melting Point

300 °C with decomposition

5 Chemical Vendors

6 Drug and Medication Information

6.1 Drug Indication

Investigated for use/treatment in liver disease and pulmonary fibrosis.

6.2 Clinical Trials

6.2.1 ClinicalTrials.gov

7 Pharmacology and Biochemistry

7.1 Pharmacodynamics

Tetrathiomolybdate demonstrated the ability to reduce toxic free copper levels and substantially improve clinical neurologic outcomes in Wilson’s patients. Studies also showed it is capable of specifically inhibiting chronic fibrotic disease processes in the lung.

7.2 MeSH Pharmacological Classification

Angiogenesis Inhibitors
Agents and endogenous substances that antagonize or inhibit the development of new blood vessels. (See all compounds classified as Angiogenesis Inhibitors.)
Chelating Agents
Chemicals that bind to and remove ions from solutions. Many chelating agents function through the formation of COORDINATION COMPLEXES with METALS. (See all compounds classified as Chelating Agents.)
Enzyme Inhibitors
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. (See all compounds classified as Enzyme Inhibitors.)

7.3 Mechanism of Action

Tetrathiomolybdate has demonstrated the ability to inhibit fibrosis in a number of well established animal models through the sequestration of available copper and inhibition of key fibrotric cytokines, including secreted protein acid rich in cysteine (SPARC), NFkappaB, TGF-beta, FGF-2, IL-1, IL-6, IL-8, and connective tissue growth factor (CTGF).

8 Toxicity

8.1 Toxicological Information

8.1.1 Acute Effects

9 Associated Disorders and Diseases

10 Literature

10.1 Consolidated References

10.2 NLM Curated PubMed Citations

10.3 Chemical Co-Occurrences in Literature

10.4 Chemical-Gene Co-Occurrences in Literature

10.5 Chemical-Disease Co-Occurrences in Literature

11 Patents

11.1 Depositor-Supplied Patent Identifiers

11.2 Chemical Co-Occurrences in Patents

11.3 Chemical-Disease Co-Occurrences in Patents

11.4 Chemical-Gene Co-Occurrences in Patents

12 Interactions and Pathways

12.1 Protein Bound 3D Structures

12.1.1 Ligands from Protein Bound 3D Structures

PDBe Ligand Code
PDBe Structure Code
PDBe Conformer

12.2 Chemical-Target Interactions

12.3 Drug-Drug Interactions

13 Biological Test Results

13.1 BioAssay Results

14 Classification

14.1 MeSH Tree

14.2 NCI Thesaurus Tree

14.3 ChEBI Ontology

14.4 ChemIDplus

14.5 MolGenie Organic Chemistry Ontology

15 Information Sources

  1. ChEBI
  2. DrugBank
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    https://www.drugbank.ca/legal/terms_of_use
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    LICENSE
    Unless otherwise indicated, all text within NCI products is free of copyright and may be reused without our permission. Credit the National Cancer Institute as the source.
    https://www.cancer.gov/policies/copyright-reuse
  4. ChemIDplus
    ChemIDplus Chemical Information Classification
    https://pubchem.ncbi.nlm.nih.gov/source/ChemIDplus
  5. FDA Global Substance Registration System (GSRS)
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  6. ClinicalTrials.gov
    LICENSE
    The ClinicalTrials.gov data carry an international copyright outside the United States and its Territories or Possessions. Some ClinicalTrials.gov data may be subject to the copyright of third parties; you should consult these entities for any additional terms of use.
    https://clinicaltrials.gov/ct2/about-site/terms-conditions#Use
  7. Comparative Toxicogenomics Database (CTD)
    LICENSE
    It is to be used only for research and educational purposes. Any reproduction or use for commercial purpose is prohibited without the prior express written permission of NC State University.
    http://ctdbase.org/about/legal.jsp
  8. Therapeutic Target Database (TTD)
  9. European Chemicals Agency (ECHA)
    LICENSE
    Use of the information, documents and data from the ECHA website is subject to the terms and conditions of this Legal Notice, and subject to other binding limitations provided for under applicable law, the information, documents and data made available on the ECHA website may be reproduced, distributed and/or used, totally or in part, for non-commercial purposes provided that ECHA is acknowledged as the source: "Source: European Chemicals Agency, http://echa.europa.eu/". Such acknowledgement must be included in each copy of the material. ECHA permits and encourages organisations and individuals to create links to the ECHA website under the following cumulative conditions: Links can only be made to webpages that provide a link to the Legal Notice page.
    https://echa.europa.eu/web/guest/legal-notice
  10. Protein Data Bank in Europe (PDBe)
  11. Wikidata
  12. PubChem
  13. Medical Subject Headings (MeSH)
    LICENSE
    Works produced by the U.S. government are not subject to copyright protection in the United States. Any such works found on National Library of Medicine (NLM) Web sites may be freely used or reproduced without permission in the U.S.
    https://www.nlm.nih.gov/copyright.html
  14. MolGenie
    MolGenie Organic Chemistry Ontology
    https://github.com/MolGenie/ontology/
CONTENTS