GALLIUM CATION

US Previously Marketed

Details

Stereochemistry	ACHIRAL
Molecular Formula	Ga
Molecular Weight	69.723
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	3

SHOW SMILES / InChI

Structure Search

SMILES

[Ga+3]

InChI

InChIKey=CKHJYUSOUQDYEN-UHFFFAOYSA-N

InChI=1S/Ga/q+3

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Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/019961_S009_GANITE.pdf | https://www.ncbi.nlm.nih.gov/pubmed/12776257

Gallium nitrate (brand name Ganite) is a drug that is used to treat hyper-calcemia, or too much calcium in the blood. Ganite exerts a hypocalcemic effect by inhibiting calcium resorption from bone, possibly by reducing increased bone turnover. It was shown, that gallium favorably altered the mineral properties to enhance hydroxyapatite crystallization and reduced mineral solubility. The drug also acted on the cellular components of bone to reduce bone resorption by decreasing acid secretion by osteoclasts. Nevertheless, ganite was withdrawn from sale, although the reasons was not the safety or effectiveness. Gallium nitrate inhibits the growth of various lymphoma cell lines in vitro and exhibits antitumor activity in patients with lymphoma. Gallium binds avidly to the iron transport protein transferrin. Transferrin-gallium complexes preferentially target cells that express transferrin receptors on their surface. Expression of transferrin receptors is particularly high on lymphoma cells. Cellular uptake of the gallium-transferrin complex leads to inhibition of cellular proliferation primarily via disruption of iron transport and homeostasis and blockade of ribonucleotide reductase. In phase II of clinical trials in patients with relapsed or refractory lymphoma, the antitumor activity of gallium nitrate is similar to, or better than, that of other commonly used chemotherapeutic agents.

CNS Activity

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Serotransferrin 12 Target ID: CHEMBL4865 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16988841\|https://www.ncbi.nlm.nih.gov/pubmed/15651176	Binding Agent 1064
Ribonucleoside-diphosphate reductase RR1 14 Target ID: CHEMBL2095215 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12776257\|https://www.ncbi.nlm.nih.gov/pubmed/1335254\|https://www.ncbi.nlm.nih.gov/pubmed/15651176\|https://www.ncbi.nlm.nih.gov/pubmed/22800370	Inhibitor 8297
Interleukin-1 beta 22 Target ID: P01584 Gene ID: 3553.0 Gene Symbol: IL1B Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/10727770\|https://www.ncbi.nlm.nih.gov/pubmed/16122880	Inhibitor 8297
Ribonucleoside-diphosphate reductase RR1 14 Target ID: CHEMBL2095215 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12776257	Inhibitor 8297
Hydroxyapatite 20 Target ID: CHEMBL2363055 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12776254	Modulator 828

Conditions

Condition	Modality	Highest Phase	Product
Cancer-related hypercalcemia 12 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/019961_S009_GANITE.pdf	Primary	Approved 8429	GANITE Approved Use Ganite is indicated for the treatment of clearly symptomatic cancer-related hypercalcemia that has not responded to adequate hydration. In general, patients with a serum calcium (corrected for albumin) < 12 mg/dL would not be expected to be symptomatic. Mild or asymptomatic hypercalcemia may be treated with conservative measures (i.e., saline hydration, with or without diuretics). In the treatment of cancer-related hypercalcemia, it is important first to establish adequate hydration, preferably with intravenous saline, in order to increase the renal excretion of calcium and correct dehydration caused by hypercalcemia. Launch Date 6.6407039E11
Non-Hodgkin's lymphoma 79 Sources: https://clinicaltrials.gov/ct2/show/NCT00054808	Primary	Phase III 656	Unknown Approved Use Unknown
Relapsed or refractory lymphoma 12 Sources: https://clinicaltrials.gov/ct2/show/NCT00054808	Primary	Phase II 1132	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Effects of gallium nitrate on calcium transients in UMR-106 rat osteoblastic osteosarcoma cells.	1992	1419379
Management of acute hypercalcemia.	1992 Apr 30	1532633
Long-term effects of gallium nitrate in patients with Paget's disease of bone.	1992 Oct	1456092
Non-iron metalloporphyrins: potent antibacterial compounds that exploit haem/Hb uptake systems of pathogenic bacteria.	1999 Jan	10027961
Effects of trace metal compounds on HIV-1 reverse transcriptase: an in vitro study.	1999 May	10327022
Role for an essential tyrosine in peptide amidation.	2006 Jul 28	16704972
Gallium nitrate is efficacious in murine models of tuberculosis and inhibits key bacterial Fe-dependent enzymes.	2013 Dec	24060870
Serum and tissue concentrations of gallium after oral administration of gallium nitrate and gallium maltolate to neonatal calves.	2016 Feb	27027708

Patents

Sample Use Guides

In Vivo Use Guide

The usual recommended dose of Ganite (Gallium nitrate injection) is 200 mg per square meter of body surface area (200 mg/m2) daily for 5 consecutive days. In patients with mild hypercalcemia and few symptoms, a lower dosage of 100 mg/m2/day for 5 days may be considered. If serum calcium levels are lowered into the normal range in less than 5 days, treatment may be discontinued early. The daily dose must be administered as an intravenous infusion over 24 hours. Controlled studies have not been undertaken to evaluate the safety and effectiveness of retreatment with gallium nitrate. When Ganite is added to either 0.9% Sodium Chloride Injection USP or 5% Dextrose Injection USP, it is stable for 48 hours at room temperature (15°C to 30°C) or for 7 days if stored under refrigeration (2°C to 8°C). Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

Route of Administration: Intravenous

In Vitro Use Guide

Because bladder cancer has many transferrin (Tf) receptors and gallium has been reported to bind avidly with Tf receptors, gallium cytotoxicity and the possibility of intravesical instillation therapy with gallium nitrate were studied in vitro. The bladder cancer cell lines J82, 639V, VMCuB1, SCaBER, and 5637 were used. The amount of Tf receptor was checked by a rosette assay. As a cytotoxicity assay, two experimental models were tested using two or 72 hours of exposure to gallium solution. For 72 hours of exposure at gallium concentrations above 250 mumol/L, the inhibitory effect was a function of gallium concentration, and 100% cytotoxicity occurred at 2 mmol/L. At lower concentrations of gallium, the effect was related to the amount of Tf and the level of Tf receptor expression of the cells. With two hours of exposure, which was assumed to be a model of intravesical therapy, the inhibitory effect increased in proportion to gallium concentration and the frequency of treatment. Twenty mmol/L gallium effectively inhibited the growth in two hours of exposure.

Name

Type

Language

GALLIUM CATION

Common Name

English

GALLIUM (GA3+)

Common Name

English

GALLIUM(III) CATION

Common Name

English

GALLIUM(3+) CATION

Common Name

English

GALLIUM, ION (GA3+)

Common Name

English

GA3+

Common Name

English

GALLIUM ION(3+)

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C597