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Record Information
Creation Date2005-11-16 15:48:42 UTC
Update Date2017-08-15 22:05:17 UTC
Secondary Accession Numbers
  • HMDB01478
Metabolite Identification
Common NameGallium
DescriptionDiscovered in 1875, gallium is a trivalent metal that shares certain chemical characteristics with Fe 3+, Al3+ and In3+. An important property of gallium is its high affinity binding to transferrin, the iron transport protein in the circulation. Approximately one third of transferrin in blood is occupied by iron, leaving the remainder free to bind and transport gallium to cells that display transferrin receptors. In support of this mechanism is the finding that during radiogallium tumor imaging (Ga-67 scanning) in patients, Ga-67 in the circulation is bound almost exclusively to transferrin. A recent study examining the distribution of nonradioactive gallium in the circulation after its gastrointestinal uptake from gallium maltolate (an oral formulation of gallium) has confirmed that it binds to transferrin. The cellular uptake of gallium (transferrin-gallium) is mediated primarily by cell surface transferrin receptors, although a small amount of gallium may also be incorporated into cells via transferrin dependent mechanisms. Transferrin receptors are normally present on erythroid progenitor cells in the marrow to facilitate cellular iron uptake for hemoglobin synthesis. However, transferrin receptors are also expressed in high density on proliferating cells, because iron is needed for the activity of ribonucleotide reductase, the enzyme responsible for deoxyribonucleotide synthesis. In particular, transferrin receptors are expressed on non Hodgkin lymphoma (NHL) and bladder cancer cells (but not on their normal counterparts), making them obvious targets for gallium. Although the transferrin mediated delivery of gallium to cancer cells appears to be an important initial step in its antineoplastic action, the downstream events leading to cell death are only partly understood. At the cell surface, transferrin gallium competes with transferrin iron for entry into the cell. Inside the cell, endosomal acidification, essential for the release of iron from transferrin, is perturbed by gallium. Hence, gallium disrupts cellular iron homeostasis. The gallium induced block in cellular iron uptake, coupled with a direct effect of intracellular gallium, leads to inhibition of the iron-dependent R2 subunit of ribonucleotide reductase and an arrest in DNA synthesis. The nature of gallium-induced cell death was first reported by Haq et al. who demonstrated the induction of DNA fragmentation and morphologic changes consistent with apoptosis in lymphoma cells exposed to gallium nitrate. More recently, gallium nitrate was shown to induce apoptosis through the intrinsic pathway involving Bax, mitochondrial release of cytochrome c, and caspase-3 activation. The molecular basis for tumor cell resistance to gallium is not understood. It is not the result of an increase in ribonucleotide reductase activity, but it may be related to decreased cellular gallium incorporation. A complementary DNA microarray analysis of gallium resistant and gallium sensitive lymphoma cell lines has suggested that gallium resistance may involve changes in proteins responsible for intracellular trafficking. The action of gallium extends to other pathologic conditions in which cellular transferrin receptors are increased. Mitogen activated T and B cells express transferrin receptors; the proliferation of these cells, along with immunoglobulin production by B cells, can be inhibited by gallium. Gallium nitrate has been shown to have immunosuppressive activity in animal models of graft-versus-host disease following bone marrow transplantation, adjuvant arthritis, cardiac transplant rejection, and allergic autoimmune encephalomyelitis. The trivalent gallium cation is capable of inhibiting tumor growth, mainly because of its resemblance to ferric iron. It affects cellular acquisition of iron by binding to transferrin, and it interacts with the iron-dependent enzyme ribonucleotide reductase, resulting in reduced dNTP pools and inhibition of DNA synthesis. The abundance of transferrin receptors and the up regulation of ribonucleotide reductase render tumor cells susceptible to the cytotoxicity of gallium. Remarkable clinical activity in lymphomas and bladder cancer has been documented in clinical studies employing intravenous gallium nitrate, which is currently being re-evaluated in non-Hodgkin's lymphoma. (PMID: 15579097 , 15627016 )
Chemical FormulaGaH3
Average Molecular Weight72.747
Monoisotopic Molecular Weight71.949056008
IUPAC Namegallane
Traditional Namegallane
CAS Registry Number7440-55-3
InChI Identifier
Chemical Taxonomy
DescriptionThis compound belongs to the class of chemical entities known as miscellaneous mixed metal/non-metals. These are inorganic compounds containing non-metal as well as metal atoms but not belonging to afore mentioned classes.
KingdomChemical entities
Super ClassInorganic compounds
ClassMixed metal/non-metal compounds
Sub ClassMiscellaneous mixed metal/non-metals
Direct ParentMiscellaneous mixed metal/non-metals
Alternative ParentsNot Available
  • Miscellaneous mixed metal/non-metal
Molecular FrameworkNot Available
External Descriptors
StatusDetected and Quantified
BiofunctionNot Available
ApplicationNot Available
Cellular locationsNot Available
Physical Properties
Experimental Properties
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
Physiological Charge0ChemAxon
Hydrogen Acceptor Count0ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area0 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity2.4 m3·mol-1ChemAxon
Polarizability3.42 Å3ChemAxon
Number of Rings0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
SpectraNot Available
Biological Properties
Cellular LocationsNot Available
Biofluid Locations
  • Cerebrospinal Fluid (CSF)
  • Saliva
  • Urine
Tissue LocationNot Available
PathwaysNot Available
Normal Concentrations
Cerebrospinal Fluid (CSF)Detected and Quantified<0.0005 uMAdult (>18 years old)BothNormal details
SalivaDetected and Quantified0.028 +/- 0.009 uMAdult (>18 years old)BothNormal
    • Zerihun T. Dame, ...
UrineDetected and Quantified0.0056 (0.0012-0.0150) umol/mmol creatinineAdult (>18 years old)Both
UrineDetected and Quantified0.0002 +/- 0.0002 umol/mmol creatinineAdult (>18 years old)Not SpecifiedNormal details
UrineDetected and Quantified0.0003 - 0.0006 umol/mmol creatinineAdult (>18 years old)Not SpecifiedNormal details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDNot Available
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider IDNot Available
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkNot Available
NuGOwiki LinkHMDB0001478
METLIN IDNot Available
PubChem CompoundNot Available
PDB IDNot Available
ChEBI ID33326
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. Jakupec MA, Keppler BK: Gallium in cancer treatment. Curr Top Med Chem. 2004;4(15):1575-83. [PubMed:15579097 ]
  2. Chitambar CR: Gallium compounds as antineoplastic agents. Curr Opin Oncol. 2004 Nov;16(6):547-52. [PubMed:15627016 ]