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IdentificationPharmacologyInteractionsReferencesTrialsEconomicsPropertiesSpectraTaxonomyGallium nitrate
Identification
- Name
- Gallium nitrate
- Accession Number
- DB05260
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Description
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
Structure for DB05260 (Gallium nitrate)
- 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 - Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Ganite Injection, solution, concentrate 25 mg/mL Intravenous Genta Incorporated 2003-09-17 2017-07-26 US 
- 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
- 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 inhibitorHuman AV-type proton ATPase subunit B, brain isoform inhibitorHuman AOsteocalcin antagonistHuman AHydroxylapatite modulatorHuman UProtein-tyrosine-phosphatase inhibitorShewanella sp. AInterleukin-1 beta antagonistHuman - 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 Drug group Acetyldigitoxin Acetyldigitoxin may decrease the cardiotoxic activities of Gallium nitrate. Approved Acetyldigoxin Acetyldigoxin may decrease the cardiotoxic activities of Gallium nitrate. Experimental Ancestim The risk or severity of cytotoxicity can be increased when Ancestim is combined with Gallium nitrate. Approved, Investigational, Withdrawn Anthrax immune globulin human The risk or severity of adverse effects can be increased when Gallium nitrate is combined with Anthrax immune globulin human. Approved Bacillus calmette-guerin substrain connaught live antigen The risk or severity of adverse effects can be increased when Gallium nitrate is combined with Bacillus calmette-guerin substrain connaught live antigen. Approved, Investigational Bacillus calmette-guerin substrain tice live antigen The risk or severity of adverse effects can be increased when Gallium nitrate is combined with Bacillus calmette-guerin substrain tice live antigen. Approved BCG vaccine The therapeutic efficacy of BCG vaccine can be decreased when used in combination with Gallium nitrate. Investigational Bevacizumab Bevacizumab may increase the cardiotoxic activities of Gallium nitrate. Approved, Investigational Cabazitaxel The risk or severity of adverse effects can be increased when Cabazitaxel is combined with Gallium nitrate. Approved Clostridium tetani toxoid antigen (formaldehyde inactivated) The risk or severity of adverse effects can be increased when Gallium nitrate is combined with Clostridium tetani toxoid antigen (formaldehyde inactivated). Approved Corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated) The risk or severity of adverse effects can be increased when Gallium nitrate is combined with Corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated). Approved Cyclophosphamide Cyclophosphamide may increase the cardiotoxic activities of Gallium nitrate. Approved, Investigational Cymarin Cymarin may decrease the cardiotoxic activities of Gallium nitrate. Experimental Denosumab The risk or severity of adverse effects can be increased when Denosumab is combined with Gallium nitrate. Approved Deslanoside Deslanoside may decrease the cardiotoxic activities of Gallium nitrate. Approved Digitoxin Digitoxin may decrease the cardiotoxic activities of Gallium nitrate. Approved, Investigational Digoxin Digoxin may decrease the cardiotoxic activities of Gallium nitrate. Approved Digoxin Immune Fab (Ovine) Digoxin Immune Fab (Ovine) may decrease the cardiotoxic activities of Gallium nitrate. Approved Docetaxel The risk or severity of adverse effects can be increased when Docetaxel is combined with Gallium nitrate. Approved, Investigational Fingolimod Gallium nitrate may increase the immunosuppressive activities of Fingolimod. Approved, Investigational G17DT The risk or severity of adverse effects can be increased when Gallium nitrate is combined with G17DT. Investigational GI-5005 The risk or severity of adverse effects can be increased when Gallium nitrate is combined with GI-5005. Investigational Gitoformate Gitoformate may decrease the cardiotoxic activities of Gallium nitrate. Experimental Hepatitis A Vaccine The risk or severity of adverse effects can be increased when Gallium nitrate is combined with Hepatitis A Vaccine. Approved Hepatitis B Vaccine (Recombinant) The risk or severity of adverse effects can be increased when Gallium nitrate is combined with Hepatitis B Vaccine (Recombinant). Approved, Withdrawn Human rabies virus immune globulin The risk or severity of adverse effects can be increased when Gallium nitrate is combined with Human rabies virus immune globulin. Approved INGN 201 The risk or severity of adverse effects can be increased when Gallium nitrate is combined with INGN 201. Investigational INGN 225 The risk or severity of adverse effects can be increased when Gallium nitrate is combined with INGN 225. Investigational Japanese encephalitis virus strain sa 14-14-2 antigen (formaldehyde inactivated) The risk or severity of adverse effects can be increased when Gallium nitrate is combined with Japanese encephalitis virus strain sa 14-14-2 antigen (formaldehyde inactivated). Approved Lanatoside C Lanatoside C may decrease the cardiotoxic activities of Gallium nitrate. Experimental Leflunomide The risk or severity of adverse effects can be increased when Gallium nitrate is combined with Leflunomide. Approved, Investigational Metildigoxin Metildigoxin may decrease the cardiotoxic activities of Gallium nitrate. Experimental Natalizumab The risk or severity of adverse effects can be increased when Gallium nitrate is combined with Natalizumab. Approved, Investigational Ocrelizumab Ocrelizumab may increase the immunosuppressive activities of Gallium nitrate. Approved, Investigational Oleandrin Oleandrin may decrease the cardiotoxic activities of Gallium nitrate. Experimental, Investigational Ouabain Ouabain may decrease the cardiotoxic activities of Gallium nitrate. Approved Paclitaxel The risk or severity of adverse effects can be increased when Paclitaxel is combined with Gallium nitrate. Approved, Vet Approved Peruvoside Peruvoside may decrease the cardiotoxic activities of Gallium nitrate. Experimental Pimecrolimus The risk or severity of adverse effects can be increased when Pimecrolimus is combined with Gallium nitrate. Approved, Investigational Proscillaridin Proscillaridin may decrease the cardiotoxic activities of Gallium nitrate. Experimental Rabies virus inactivated antigen, A The risk or severity of adverse effects can be increased when Gallium nitrate is combined with Rabies virus inactivated antigen, A. Approved, Investigational Rabies virus inactivated antigen, A The therapeutic efficacy of Rabies virus inactivated antigen, A can be decreased when used in combination with Gallium nitrate. Approved, Investigational Rindopepimut The risk or severity of adverse effects can be increased when Gallium nitrate is combined with Rindopepimut. Investigational Roflumilast Roflumilast may increase the immunosuppressive activities of Gallium nitrate. Approved Rotavirus Vaccine The risk or severity of adverse effects can be increased when Gallium nitrate is combined with Rotavirus Vaccine. Approved Rubella virus vaccine The risk or severity of adverse effects can be increased when Gallium nitrate is combined with Rubella virus vaccine. Approved, Investigational Salmonella typhi ty2 vi polysaccharide antigen The risk or severity of adverse effects can be increased when Gallium nitrate is combined with Salmonella typhi ty2 vi polysaccharide antigen. Approved Salmonella typhi ty21a live antigen The risk or severity of adverse effects can be increased when Gallium nitrate is combined with Salmonella typhi ty21a live antigen. Approved Sipuleucel-T The therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Gallium nitrate. Approved, Investigational SRP 299 The risk or severity of adverse effects can be increased when Gallium nitrate is combined with SRP 299. Investigational Tacrolimus Tacrolimus may increase the immunosuppressive activities of Gallium nitrate. Approved, Investigational Tecemotide The risk or severity of adverse effects can be increased when Gallium nitrate is combined with Tecemotide. Investigational TG4010 The risk or severity of adverse effects can be increased when Gallium nitrate is combined with TG4010. Investigational Tofacitinib Gallium nitrate may increase the immunosuppressive activities of Tofacitinib. Approved, Investigational Trastuzumab Trastuzumab may increase the cardiotoxic activities of Gallium nitrate. Approved, Investigational Typhoid Vaccine The risk or severity of adverse effects can be increased when Gallium nitrate is combined with Typhoid Vaccine. Approved Varicella Zoster Vaccine (Live/Attenuated) The risk or severity of adverse effects can be increased when Gallium nitrate is combined with Varicella Zoster Vaccine (Live/Attenuated). Approved Yellow Fever Vaccine The risk or severity of adverse effects can be increased when Gallium nitrate is combined with Yellow Fever Vaccine. Approved, Investigational - 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
- Drugs.com
- Drugs.com Drug Page
- 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/mL - 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
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
- Kind
- Protein
- Organism
- Human
- 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]
- Kind
- Protein
- Organism
- Human
- 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]
- Kind
- Protein
- Organism
- Human
- 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]
Yes
Modulator
References
- Bockman R: The effects of gallium nitrate on bone resorption. Semin Oncol. 2003 Apr;30(2 Suppl 5):5-12. [PubMed:12776254]
- 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]
- Kind
- Protein
- Organism
- Human
- 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
- Kind
- Protein
- Organism
- Human
- 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
- Kind
- Protein group
- Organism
- Human
- 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:
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 July 02, 2018 20:51