Preferred Label : Tetrathiomolybdate;
NCIt synonyms : TM; Molybdate(2-), Tetrathioxo-, (T-4)- (9CI); Tetrathioxomolybdate(2-);
NCIt related terms : TIOMOLIBDATE ION;
NCIt definition : 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.;
UNII : 91U3TGV99T;
InChIKey : CXVCSRUYMINUSF-UHFFFAOYSA-N;
CAS number : 16330-92-0;
Molecule name : CCRIS 9412;
NCI Metathesaurus CUI : CL969619;
Origin ID : C160684;
UMLS CUI : C0076339;
Currated CISMeF NLP mapping
- Semantic type(s)
- UMLS correspondences (same concept)
- concept_is_in_subset
