| Identification |
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| Name | Gallium nitrate |
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| Accession Number | DB05260 |
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| Type | Small Molecule |
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| Groups | Approved, Investigational |
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| 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.
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| Structure | |
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| Synonyms | | Gallium nitrate (anhydrous) | | Nitric acid, gallium salt, anhydrate |
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| External IDs | Not Available |
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| Product Ingredients | |
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| Approved Prescription Products | | Name | Dosage | Strength | Route | Labeller | Marketing Start | Marketing End | | | Ganite | Injection, solution, concentrate | 25 mg/mL | Intravenous | Genta Incorporated | 2003-09-17 | Not applicable | US |
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| Approved Generic Prescription Products | Not Available |
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| Approved Over the Counter Products | Not Available |
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| Unapproved/Other Products | Not Available |
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| International Brands | Not Available |
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| Brand mixtures | Not Available |
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| Categories | |
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| UNII | Y2V2R4W9TQ |
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| CAS number | 13494-90-1 |
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| Weight | Average: 255.738
Monoisotopic: 254.889034525 |
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| Chemical Formula | GaN3O9 |
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| InChI Key | CHPZKNULDCNCBW-UHFFFAOYSA-N |
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| InChI | InChI=1S/Ga.3NO3/c;3*2-1(3)4/q+3;3*-1 |
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| IUPAC Name | gallium(3+) ion trinitrate |
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| SMILES | [Ga+3].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O |
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| Pharmacology |
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| Indication | For the treatment of hypercalcemia. Also intended for the treatment of non-hodgkin's lymphoma.
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| Structured Indications | |
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| 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.
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| 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 | Kind | Pharmacological action | Actions | Organism | UniProt ID | |
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| Ribonucleoside-diphosphate reductase subunit M2 | Protein | yes | inhibitor | Human | P31350 | details | | V-type proton ATPase subunit B, brain isoform | Protein | yes | inhibitor | Human | P21281 | details | | Osteocalcin | Protein | yes | antagonist | Human | P02818 | details | | Hydroxylapatite | Small molecule | yes | modulator | Human | not applicable | details | | Protein-tyrosine-phosphatase | Protein | unknown | inhibitor | Shewanella sp. | Q9S427 | details | | Interleukin-1 beta | Protein | yes | antagonist | Human | P01584 | details |
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| Related Articles | |
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| Absorption | Not Available |
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| Volume of distribution | Not Available |
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| Protein binding | Not Available |
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| Metabolism | Not Available |
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| Route of elimination | Gallium nitrate is not metabolized either by the liver or the kidney and appears to be significantly excreted via the kidney.
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| Half life | Alpha: 1 hour. Beta: 24 hours, but lengthens to 72 to 115 hours with prolonged intravenous infusion.
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| 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]
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| Toxicity | Not Available |
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| Affected organisms | |
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| Pathways | Not Available |
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| Pharmacogenomic Effects/ADRs | Not Available |
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| Interactions |
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| Drug Interactions | | Drug | Interaction | Drug group |
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| Acetyldigitoxin | Acetyldigitoxin may decrease the cardiotoxic activities of Gallium nitrate. | Approved | | 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 | | Cyclophosphamide | Cyclophosphamide may increase the cardiotoxic activities of Gallium nitrate. | Approved, Investigational | | 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 | | Digoxin | Digoxin 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 | | 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 | | Leflunomide | The risk or severity of adverse effects can be increased when Gallium nitrate is combined with Leflunomide. | Approved, Investigational | | Natalizumab | The risk or severity of adverse effects can be increased when Gallium nitrate is combined with Natalizumab. | Approved, Investigational | | Oleandrin | Anvirzel may decrease the cardiotoxic activities of Gallium nitrate. | Experimental | | 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 | | Pimecrolimus | The risk or severity of adverse effects can be increased when Pimecrolimus is combined with Gallium nitrate. | Approved, Investigational | | Rindopepimut | The risk or severity of adverse effects can be increased when Gallium nitrate is combined with CDX-110. | Investigational | | Roflumilast | Roflumilast may increase the immunosuppressive activities of Gallium nitrate. | Approved | | Sipuleucel-T | The therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Gallium nitrate. | Approved | | SRP 299 | The risk or severity of adverse effects can be increased when Gallium nitrate is combined with SRP 299. | Investigational | | Tacrolimus | The risk or severity of adverse effects can be increased when Tacrolimus is combined with Gallium nitrate. | Approved, 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 |
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| Food Interactions | Not Available |
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| References |
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| Synthesis Reference | Not Available |
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| 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 ]
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| External Links | |
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| ATC Codes | Not Available |
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| AHFS Codes | Not Available |
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| PDB Entries | Not Available |
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| FDA label | Not Available |
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| MSDS | Download (8.19 KB) |
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| Clinical Trials |
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| Clinical Trials | |
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| Pharmacoeconomics |
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| Manufacturers | Not Available |
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| Packagers | Not Available |
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| Dosage forms | | Form | Route | Strength |
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| Injection, solution, concentrate | Intravenous | 25 mg/mL |
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| Prices | Not Available |
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| Patents | Not Available |
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| Properties |
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| State | Solid |
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| Experimental Properties | Not Available |
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| Predicted Properties | |
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| Predicted ADMET features | | Property | Value | Probability |
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| 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 ) |
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| Spectra |
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| Mass Spec (NIST) | Not Available |
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| Spectra | Not Available |
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| Taxonomy |
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| Description | This compound belongs to the class of chemical entities 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. |
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| Kingdom | Chemical entities |
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| Super Class | Inorganic compounds |
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| Class | Mixed metal/non-metal compounds |
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| Sub Class | Post-transition metal oxoanionic compounds |
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| Direct Parent | Post-transition metal nitrates |
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| Alternative Parents | Post-transition metal salts / Inorganic salts / Inorganic oxides |
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| Substituents | Post-transition metal nitrate / Inorganic post-transition metal salt / Inorganic oxide / Inorganic salt |
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| Molecular Framework | Not Available |
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| External Descriptors | Not Available |
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