Tetrathiomolybdate

Identification

Name
Tetrathiomolybdate
Accession Number
DB05088
Type
Small Molecule
Groups
Investigational
Description

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.

Structure
Thumb
Synonyms
  • Thiomolybdate
  • Tiomolibdate ion
External IDs
ATN-224
International/Other Brands
Copexa / Coprexa
Categories
UNII
91U3TGV99T
CAS number
16330-92-0
Weight
Average: 224.19
Monoisotopic: 225.794787
Chemical Formula
MoS4
InChI Key
CXVCSRUYMINUSF-UHFFFAOYSA-N
InChI
InChI=1S/Mo.4S/q;;;2*-1
IUPAC Name
(sulfanidyldisulfanylidenemolybdenio)sulfanide
SMILES
[S-][Mo]([S-])(=S)=S

Pharmacology

Indication

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

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.

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).

TargetActionsOrganism
UAmyloid beta A4 proteinNot AvailableHumans
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
Technetium Tc-99m oxidronateTiomolibdate ion may decrease effectiveness of Technetium Tc-99m oxidronate as a diagnostic agent.
Food Interactions
Not Available

References

General References
Not Available
External Links
PubChem Compound
25199766
PubChem Substance
175426941
ChemSpider
10619308
ChEBI
30703
HET
4SM
Wikipedia
Tetrathiomolybdate
PDB Entries
3k7r

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
1, 2CompletedTreatmentIdiopathic Pulmonary Fibrosis (IPF)1
1, 2TerminatedTreatmentMultiple Myeloma (MM)1
2Active Not RecruitingTreatmentCancer, Breast1
2CompletedTreatmentCarcinoma, Colorectal1
2CompletedTreatmentHepatocellular,Carcinoma1
2CompletedTreatmentOesophageal Carcinoma1
2CompletedTreatmentProstate Cancer1
2CompletedTreatmentPsoriasis1
2Unknown StatusTreatmentMelanoma1
2Unknown StatusTreatmentProstate Cancer1
3CompletedTreatmentPrimary Biliary Cholangitis1
3CompletedTreatmentWilson's Disease1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)300 °C with decompositionNot Available
Predicted Properties
PropertyValueSource
logP1.57ChemAxon
pKa (Strongest Acidic)9.2ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count0ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area0 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity37.74 m3·mol-1ChemAxon
Polarizability14.29 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.8526
Blood Brain Barrier+0.9565
Caco-2 permeable+0.5325
P-glycoprotein substrateNon-substrate0.8815
P-glycoprotein inhibitor INon-inhibitor0.9718
P-glycoprotein inhibitor IINon-inhibitor0.9958
Renal organic cation transporterNon-inhibitor0.9404
CYP450 2C9 substrateNon-substrate0.8471
CYP450 2D6 substrateNon-substrate0.8348
CYP450 3A4 substrateNon-substrate0.7961
CYP450 1A2 substrateNon-inhibitor0.7649
CYP450 2C9 inhibitorNon-inhibitor0.7287
CYP450 2D6 inhibitorNon-inhibitor0.9226
CYP450 2C19 inhibitorNon-inhibitor0.8342
CYP450 3A4 inhibitorNon-inhibitor0.9357
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7635
Ames testNon AMES toxic0.7926
CarcinogenicityCarcinogens 0.6589
BiodegradationNot ready biodegradable0.9497
Rat acute toxicity2.4587 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9173
hERG inhibition (predictor II)Non-inhibitor0.9494
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Classification
Not classified

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Transition metal ion binding
Specific Function
Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Involved in cell mobility and tra...
Gene Name
APP
Uniprot ID
P05067
Uniprot Name
Amyloid beta A4 protein
Molecular Weight
86942.715 Da
References
  1. Venti A, Giordano T, Eder P, Bush AI, Lahiri DK, Greig NH, Rogers JT: The integrated role of desferrioxamine and phenserine targeted to an iron-responsive element in the APP-mRNA 5'-untranslated region. Ann N Y Acad Sci. 2004 Dec;1035:34-48. [PubMed:15681799]

Drug created on October 21, 2007 16:23 / Updated on March 11, 2019 12:44