Gallium nitrate is a drug that is used to treat hyper-calcemia, or too much calcium in the blood. This condition may occur when individuals develop various types of cancer. Gallium nitrate is also known by the common brand name Ganite.

Structure

Similar Structures

Synonyms

Gallium nitrate (anhydrous)
Nitric acid, gallium salt, anhydrate

Product Ingredients

Ingredient	UNII	CAS	InChI Key
Gallium nitrate nonahydrate	VRA0C6810N	135886-70-3	VALBLFFHYPYRDR-UHFFFAOYSA-N

Active Moieties

Name	Kind	UNII	CAS	InChI Key
Gallium cation	ionic	F7K5MP217W	22537-33-3	CKHJYUSOUQDYEN-UHFFFAOYSA-N

Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
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Ganite	Injection, solution, concentrate	25 mg/1mL	Intravenous	Genta Incorporated	2003-09-17	Not applicable

Additional Data Available

Application Number

A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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Product Code

A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Categories

UNII

Y2V2R4W9TQ

CAS number

13494-90-1

Weight

Average: 255.738
Monoisotopic: 254.889034525

Chemical Formula

GaN₃O₉

InChI Key

CHPZKNULDCNCBW-UHFFFAOYSA-N

InChI

InChI=1S/Ga.3NO3/c;3*2-1(3)4/q+3;3*-1

IUPAC Name

gallium(3+) ion trinitrate

SMILES

[Ga+3].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O

Pharmacology

Indication

For the treatment of hypercalcemia. Also intended for the treatment of non-hodgkin's lymphoma.

Associated Conditions

Symptomatic Hypercalcemia of malignancy

Pharmacodynamics

Gallium nitrate exerts hypocalcemic effect by inhibiting calcium resorption from bone, possibly by stabilizing bone matrix, thereby reducing increased bone turnover. Gallium nitrate inhibits the growth of various lymphoma cell lines in vitro and exhibits antitumor activity in patients with lymphoma. The mechanism(s) of cytotoxicity is (are) only partly understood but appears to involve a two-step process: (1) targeting of gallium to cells, and (2) acting on multiple, specific intracellular processes. Gallium shares certain chemical properties with iron; therefore, it 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. Recent studies have shown that cellular uptake of gallium leads to activation of caspases and induction of apoptosis. In phase II 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.

Mechanism of action

Gallium nitrate is believed to exert a hypocalcemic effect by inhibiting calcium resorption from bone. Gallium nitrate localizes preferentially where bone resorption and remodeling is occurring, and inhibits osteoclast activity. Inhibition of resorption may occur via a reduction in increased bone turnover. It seems to enhance hydroxyapatite function, inhibit osteocalcin, and inhibit the vacuolar ATPase on the osteoclast ruffled membrane. All these aid in the reduction of bone resorption.

Target	Actions	Organism
ARibonucleoside-diphosphate reductase subunit M2	inhibitor	Humans
AV-type proton ATPase subunit B, brain isoform	inhibitor	Humans
AOsteocalcin	antagonist	Humans
AHydroxylapatite	modulator	Humans
UProtein-tyrosine-phosphatase	inhibitor	Shewanella sp.
AInterleukin-1 beta	antagonist	Humans

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Adverse Effects

Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.

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Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Blackbox Warnings

Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.

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Absorption

Not Available

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism

Not Available

Route of elimination

Gallium nitrate is not metabolized either by the liver or the kidney and appears to be significantly excreted via the kidney.

Half life

Alpha: 1 hour. Beta: 24 hours, but lengthens to 72 to 115 hours with prolonged intravenous infusion.

Clearance

0.15 L/hr/kg [cancer patients receiving daily infusion of gallium nitrate at a dose of 200 mg/m2 for 5 or 7 days]

Toxicity

Not Available

Affected organisms

Humans and other mammals

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

Drug	Interaction
Unlock Additional Data
2-Methoxyethanol	The risk or severity of adverse effects can be increased when 2-Methoxyethanol is combined with Gallium nitrate.
9-(N-methyl-L-isoleucine)-cyclosporin A	The risk or severity of adverse effects can be increased when Gallium nitrate is combined with 9-(N-methyl-L-isoleucine)-cyclosporin A.
Abatacept	The risk or severity of adverse effects can be increased when Abatacept is combined with Gallium nitrate.
Abetimus	The risk or severity of adverse effects can be increased when Gallium nitrate is combined with Abetimus.
Acteoside	The risk or severity of adverse effects can be increased when Gallium nitrate is combined with Acteoside.
Adalimumab	The risk or severity of adverse effects can be increased when Adalimumab is combined with Gallium nitrate.
Adenovirus type 7 vaccine live	The risk or severity of infection can be increased when Adenovirus type 7 vaccine live is combined with Gallium nitrate.
Adenovirus type 7 vaccine live	The therapeutic efficacy of Adenovirus type 7 vaccine live can be decreased when used in combination with Gallium nitrate.
Afelimomab	The risk or severity of adverse effects can be increased when Afelimomab is combined with Gallium nitrate.
Aldesleukin	The risk or severity of adverse effects can be increased when Aldesleukin is combined with Gallium nitrate.

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Extended Description

Extended description of the mechanism of action and particular properties of each drug interaction.

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Severity

A severity rating for each drug interaction, from minor to major.

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Evidence Level

A rating for the strength of the evidence supporting each drug interaction.

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Action

An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions

Not Available

References

General References

Yang M, Kroft SH, Chitambar CR: Gene expression analysis of gallium-resistant and gallium-sensitive lymphoma cells reveals a role for metal-responsive transcription factor-1, metallothionein-2A, and zinc transporter-1 in modulating the antineoplastic activity of gallium nitrate. Mol Cancer Ther. 2007 Feb;6(2):633-43. [PubMed:17308060]
Leyland-Jones B: Treating cancer-related hypercalcemia with gallium nitrate. J Support Oncol. 2004 Nov-Dec;2(6):509-16. [PubMed:15605917]
Chitambar CR: Apoptotic mechanisms of gallium nitrate: basic and clinical investigations. Oncology (Williston Park). 2004 Nov;18(13 Suppl 10):39-44. [PubMed:15651176]
Cvitkovic F, Armand JP, Tubiana-Hulin M, Rossi JF, Warrell RP Jr: Randomized, double-blind, phase II trial of gallium nitrate compared with pamidronate for acute control of cancer-related hypercalcemia. Cancer J. 2006 Jan-Feb;12(1):47-53. [PubMed:16613662]

External Links

Human Metabolome Database: HMDB0015612
PubChem Compound: 61635
PubChem Substance: 46508923
ChemSpider: 55543
ChEMBL: CHEMBL1200983
Therapeutic Targets Database: DAP001096
PharmGKB: PA164781198
Wikipedia: Gallium_nitrate

MSDS

Download (8.19 KB)

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
1	Completed	Other	Cystic Fibrosis (CF)	1
1	Completed	Treatment	Brain and Central Nervous System Tumors / Malignant Lymphomas / Neuroblastomas / Sarcomas / Unspecified Childhood Solid Tumor, Protocol Specific	1
2	Completed	Treatment	Cystic Fibrosis (CF)	1
2	Completed	Treatment	Lymphoma, Intermediate-Grade / Lymphoma, Low-Grade / Non-Hodgkin's Lymphoma (NHL) / Refractory Lymphomas / Relapsed Lymphomas	1
2	Completed	Treatment	Malignant Lymphomas	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage forms

Form	Route	Strength
Injection, solution, concentrate	Intravenous	25 mg/1mL

Prices

Not Available

Patents

Not Available

Properties

State

Solid

Experimental Properties

Not Available

Predicted Properties

Property	Value	Source
logP	0.028	ChemAxon
pKa (Strongest Acidic)	-1.4	ChemAxon
pKa (Strongest Basic)	-6.1	ChemAxon
Physiological Charge	-1	ChemAxon
Hydrogen Acceptor Count	3	ChemAxon
Hydrogen Donor Count	0	ChemAxon
Polar Surface Area	68.88 Å²	ChemAxon
Rotatable Bond Count	0	ChemAxon
Refractivity	9.85 m³·mol^-1	ChemAxon
Polarizability	3.24 Å³	ChemAxon
Number of Rings	0	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	No	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	No	ChemAxon

Predicted ADMET features

Property	Value	Probability
Human Intestinal Absorption	+	0.7952
Blood Brain Barrier	+	0.9337
Caco-2 permeable	-	0.5678
P-glycoprotein substrate	Non-substrate	0.8817
P-glycoprotein inhibitor I	Non-inhibitor	0.927
P-glycoprotein inhibitor II	Non-inhibitor	0.984
Renal organic cation transporter	Non-inhibitor	0.9378
CYP450 2C9 substrate	Non-substrate	0.8511
CYP450 2D6 substrate	Non-substrate	0.8463
CYP450 3A4 substrate	Non-substrate	0.6475
CYP450 1A2 substrate	Non-inhibitor	0.7481
CYP450 2C9 inhibitor	Non-inhibitor	0.8894
CYP450 2D6 inhibitor	Non-inhibitor	0.9223
CYP450 2C19 inhibitor	Non-inhibitor	0.8364
CYP450 3A4 inhibitor	Non-inhibitor	0.928
CYP450 inhibitory promiscuity	Low CYP Inhibitory Promiscuity	0.9678
Ames test	AMES toxic	0.6249
Carcinogenicity	Carcinogens	0.7056
Biodegradation	Ready biodegradable	0.9392
Rat acute toxicity	2.6296 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.6413
hERG inhibition (predictor II)	Non-inhibitor	0.9681

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

Description: This compound belongs to the class of inorganic compounds known as post-transition metal nitrates. These are inorganic compounds in which the largest oxoanion is nitrate, and in which the heaviest atom not in an oxoanion is a post-transition metal.
Kingdom: Inorganic compounds
Super Class: Mixed metal/non-metal compounds
Class: Post-transition metal oxoanionic compounds
Sub Class: Post-transition metal nitrates
Direct Parent: Post-transition metal nitrates
Alternative Parents: Post-transition metal salts / Inorganic salts / Inorganic oxides
Substituents: Post-transition metal nitrate / Inorganic post-transition metal salt / Inorganic oxide / Inorganic salt
Molecular Framework: Not Available
External Descriptors: Not Available

Targets

Details1. Ribonucleoside-diphosphate reductase subunit M2

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Inhibitor

General Function: Ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor
Specific Function: Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides. Inhibits Wnt signaling.
Gene Name: RRM2
Uniprot ID: P31350
Uniprot Name: Ribonucleoside-diphosphate reductase subunit M2
Molecular Weight: 44877.25 Da

References

Chitambar CR: Apoptotic mechanisms of gallium nitrate: basic and clinical investigations. Oncology (Williston Park). 2004 Nov;18(13 Suppl 10):39-44. [PubMed:15651176]
Narasimhan J, Antholine WE, Chitambar CR: Effect of gallium on the tyrosyl radical of the iron-dependent M2 subunit of ribonucleotide reductase. Biochem Pharmacol. 1992 Dec 15;44(12):2403-8. [PubMed:1335254]
Straus DJ: Gallium nitrate in the treatment of lymphoma. Semin Oncol. 2003 Apr;30(2 Suppl 5):25-33. [PubMed:12776257]

Details2. V-type proton ATPase subunit B, brain isoform

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Inhibitor

General Function: Proton-transporting atpase activity, rotational mechanism
Specific Function: Non-catalytic subunit of the peripheral V1 complex of vacuolar ATPase. V-ATPase is responsible for acidifying a variety of intracellular compartments in eukaryotic cells.
Gene Name: ATP6V1B2
Uniprot ID: P21281
Uniprot Name: V-type proton ATPase subunit B, brain isoform
Molecular Weight: 56500.21 Da

References

Bockman R: The effects of gallium nitrate on bone resorption. Semin Oncol. 2003 Apr;30(2 Suppl 5):5-12. [PubMed:12776254]
Mattsson JP, Skyman C, Palokangas H, Vaananen KH, Keeling DJ: Characterization and cellular distribution of the osteoclast ruffled membrane vacuolar H+-ATPase B-subunit using isoform-specific antibodies. J Bone Miner Res. 1997 May;12(5):753-60. [PubMed:9144341]
Jakupec MA, Keppler BK: Gallium and other main group metal compounds as antitumor agents. Met Ions Biol Syst. 2004;42:425-62. [PubMed:15206110]

Details3. Osteocalcin

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Antagonist

General Function: Structural molecule activity
Specific Function: Constitutes 1-2% of the total bone protein. It binds strongly to apatite and calcium.
Gene Name: BGLAP
Uniprot ID: P02818
Uniprot Name: Osteocalcin
Molecular Weight: 10962.445 Da

References

Jenis LG, Waud CE, Stein GS, Lian JB, Baran DT: Effect of gallium nitrate in vitro and in normal rats. J Cell Biochem. 1993 Jul;52(3):330-6. [PubMed:8366144]
Guidon PT Jr, Salvatori R, Bockman RS: Gallium nitrate regulates rat osteoblast expression of osteocalcin protein and mRNA levels. J Bone Miner Res. 1993 Jan;8(1):103-12. [PubMed:8381250]

Details4. Hydroxylapatite

Kind

Small molecule

Organism

Humans

Pharmacological action

Yes

Actions

Modulator

References

Bockman R: The effects of gallium nitrate on bone resorption. Semin Oncol. 2003 Apr;30(2 Suppl 5):5-12. [PubMed:12776254]

Details5. Protein-tyrosine-phosphatase

Kind: Protein
Organism: Shewanella sp.
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Protein tyrosine phosphatase activity
Specific Function: Not Available
Gene Name: PPI
Uniprot ID: Q9S427
Uniprot Name: Protein-tyrosine-phosphatase
Molecular Weight: 40814.26 Da

References

Chitambar CR: Apoptotic mechanisms of gallium nitrate: basic and clinical investigations. Oncology (Williston Park). 2004 Nov;18(13 Suppl 10):39-44. [PubMed:15651176]
Berggren MM, Burns LA, Abraham RT, Powis G: Inhibition of protein tyrosine phosphatase by the antitumor agent gallium nitrate. Cancer Res. 1993 Apr 15;53(8):1862-6. [PubMed:8467506]
Straus DJ: Gallium nitrate in the treatment of lymphoma. Semin Oncol. 2003 Apr;30(2 Suppl 5):25-33. [PubMed:12776257]

Details6. Interleukin-1 beta

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Antagonist

General Function: Protein domain specific binding
Specific Function: Potent proinflammatory cytokine. Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil influx and activation, T-cell activation and cytokine production, ...
Gene Name: IL1B
Uniprot ID: P01584
Uniprot Name: Interleukin-1 beta
Molecular Weight: 30747.7 Da

References

Eby G: Elimination of arthritis pain and inflammation for over 2 years with a single 90 min, topical 14% gallium nitrate treatment: case reports and review of actions of gallium III. Med Hypotheses. 2005;65(6):1136-41. Epub 2005 Aug 24. [PubMed:16122880]

Carriers

Details1. Serotransferrin

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: Transferrin receptor binding
Specific Function: Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from si...
Gene Name: TF
Uniprot ID: P02787
Uniprot Name: Serotransferrin
Molecular Weight: 77063.195 Da

References

Groessl M, Bytzek A, Hartinger CG: The serum protein binding of pharmacologically active gallium(III) compounds assessed by hyphenated CE-MS techniques. Electrophoresis. 2009 Aug;30(15):2720-7. doi: 10.1002/elps.200800745. [PubMed:19621374]
Bernstein LR, Tanner T, Godfrey C, Noll B: Chemistry and pharmacokinetics of gallium maltolate, a compound with high oral gallium bioavailability. Met Based Drugs. 2000;7(1):33-47. doi: 10.1155/MBD.2000.33. [PubMed:18475921]
Davies NP, Suryo Rahmanto Y, Chitambar CR, Richardson DR: Resistance to the antineoplastic agent gallium nitrate results in marked alterations in intracellular iron and gallium trafficking: identification of novel intermediates. J Pharmacol Exp Ther. 2006 Apr;317(1):153-62. Epub 2005 Dec 22. [PubMed:16373528]

Transporters

Details1. Transferrin receptor (Protein Group)

Kind: Protein group
Organism: Humans
Pharmacological action: Yes

General Function: Virus receptor activity
Specific Function: Cellular uptake of iron occurs via receptor-mediated endocytosis of ligand-occupied transferrin receptor into specialized endosomes. Endosomal acidification leads to iron release. The apotransferri...

Components:

Name	UniProt ID
Transferrin receptor protein 1	P02786
Transferrin receptor protein 2	Q9UP52

References

Chitambar CR: Apoptotic mechanisms of gallium nitrate: basic and clinical investigations. Oncology (Williston Park). 2004 Nov;18(13 Suppl 10):39-44. [PubMed:15651176]

Drug created on November 18, 2007 11:22 / Updated on June 04, 2019 06:15

Gallium nitrate

Identification

Structure for Gallium nitrate (DB05260)

Pharmacology

Interactions

References

Clinical Trials

Pharmacoeconomics

Properties

Spectra

Taxonomy

Targets

References

References

References

References

References

References

Carriers

References

Transporters

Components:

References