| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
Bisphosphonate (BP), with potent anti-resorptive; RANKL
|
|---|---|
| ln Vitro |
In osteocyte-like MLO-Y4 cells, zoledronic acid disodium tetrahydrate (0.1–1 µM; 48 hours) enhances the expression of sclerostin and receptor activator of nuclear factor kB ligand (RANKL) mRNA [2]. In MLO-Y4 cells, zoledronic acid disodium tetrahydrate can upregulate the expression of factors supporting osteoclastogenesis [2]. Through the IL-6/JAK2/STAT3 pathway, zoledronic acid disodium tetrahydrate increases RANKL expression in MLO-Y4 cells [2]. By controlling the NF-κB and JNK signaling pathways, zoledronic acid disodium tetrahydrate suppresses osteoclast differentiation and function [3]. Zoledronic Acid disodium tetrahydrate (10-100 µM; 1-7 days) dramatically lowers the viability of MC3T3-E1 cells and causes them to undergo apoptosis [4]. Because it induces apoptosis, zoledronic acid disodium tetrahydrate (10–100 µM; 4 days) reduces cell viability [4]. At concentrations less than 1 µM, zoledronic acid disodium tetrahydrate prevents MC3T3-E1 cells from differentiating and maturing [4].
|
| ln Vivo |
Zoledronic acid disodium tetrahydrate (0.05 mg/kg; intraperitoneally; weekly; for 3 weeks) improves bone mineral density and content [5]. Zoledronic acid disodium tetrahydrate (0.5-1 mg/kg; i.p.; weekly; for 3 weeks) suppresses osteoclast and osteoblast function and bone remodeling in vivo, interfering with bone mechanical characteristics [5].
|
| Cell Assay |
Cell Viability Assay[4]
Cell Types: MC3T3-E1 Cell Tested Concentrations: 0.01 µM, 0.1 µM, 1 µM, 10 µM, 100 µM Incubation Duration: 1 day, 3 days, 5 days, 7 days Experimental Results: Cell viability diminished at 10 µM and 100 µM. Apoptosis analysis[4] Cell Types: MC3T3-E1 Cell Tested Concentrations: 0.01 µM, 0.1 µM, 1 µM, 10 µM, 100 µM Incubation Duration: 1 Day, 4 Days, 7 Days Experimental Results: Early Apoptotic Cells and Late Apoptosis The number of apoptotic or necrotic cells increases in a dose-dependent and time-dependent manner (high concentration). Western Blot Analysis[4] Cell Types: MC3T3-E1 Cell Tested Concentrations: 0.01 µM, 0.1 µM, 1 µM, 10 µM, 100 µM Incubation Duration: 4 days Experimental Results: The protein level of inactive caspase-3 was down-regulated and up-regulated at 10 and Regulation of protein levels of active caspase-3 at 100 µM concentration. |
| Animal Protocol |
Animal/Disease Models: Fiveweeks old C57BL6 mice [5]
Doses: 0.05 mg/kg, 0.5 mg/kg, 1 mg/kg Route of Administration: intraperitoneal (ip) injection, once a week for 3 weeks Experimental Results: Inhibition of osteoclasts and osteoblasts Osteocyte function and bone remodeling 0.5 mg/kg and 1 mg/kg. |
| Toxicity/Toxicokinetics |
Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation Because no information is available on the use of zoledronic acid during breastfeeding, an alternate drug may be preferred, especially while nursing a newborn or preterm infant. However, absorption of zoledronic acid by a breastfed infant is unlikely. ◉ Effects in Breastfed Infants Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk Relevant published information was not found as of the revision date. |
| References |
|
| Additional Infomation |
Zoledronate Disodium is the disodium salt form of zoledronate, a synthetic imidazole, third generation bisphosphonate analog of pyrophosphate with antiresorptive activity. Zoledronate binds to hydroxyapatite crystals in the bone matrix and inhibits farnesyl pyrophosphate (diphosphate) synthase, thereby preventing protein prenylation within the mevalonate pathway. This leads to the loss of downstream metabolites essential for osteoclast function, leading to the induction of apoptosis and eventually, osteoclast-cell death. By preventing osteoclast-mediated bone resorption, zoledronate decreases bone turnover and stabilizes the bone matrix.
An imidobisphosphonate inhibitor of BONE RESORPTION that is used for the treatment of malignancy-related HYPERCALCEMIA; OSTEITIS DEFORMANS; and OSTEOPOROSIS. |
| Molecular Formula |
C5H8N2O7P2-2.2[NA+].4[H2O]
|
|---|---|
| Molecular Weight |
388.11454
|
| Exact Mass |
388.002
|
| Elemental Analysis |
C, 15.47; H, 4.16; N, 7.22; Na, 11.85; O, 45.34; P, 15.96
|
| CAS # |
165800-07-7
|
| Related CAS # |
Zoledronic Acid;118072-93-8;Zoledronic acid monohydrate;165800-06-6; Zoledronic Acid;118072-93-8;Zoledronic acid disodium tetrahydrate;165800-07-7; 131654-46-1 (disodium); 165800-08-8 (trisodium hydrate); 827573-11-5 (trisodium); 165800-07-7 (disodium hydrate);
|
| PubChem CID |
23649597
|
| Appearance |
Typically exists as solid at room temperature
|
| Density |
2.13g/cm3
|
| Boiling Point |
764ºC at 760mmHg
|
| Melting Point |
305-307ºC
|
| Flash Point |
415.8ºC
|
| Vapour Pressure |
1.53E-24mmHg at 25°C
|
| Hydrogen Bond Donor Count |
7
|
| Hydrogen Bond Acceptor Count |
12
|
| Rotatable Bond Count |
4
|
| Heavy Atom Count |
22
|
| Complexity |
322
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
O.O.O.O.OC(P(=O)([O-])[O-])(P(O)(O)=O)CN1C=CN=C1.[Na+].[Na+]
|
| InChi Key |
IEJZOPBVBXAOBH-UHFFFAOYSA-L
|
| InChi Code |
InChI=1S/C5H10N2O7P2.2Na.4H2O/c8-5(15(9,10)11,16(12,13)14)3-7-2-1-6-4-7;;;;;;/h1-2,4,8H,3H2,(H2,9,10,11)(H2,12,13,14);;;4*1H2/q;2*+1;;;;/p-2
|
| Chemical Name |
Phosphonic acid, (1-hydroxy-2-(1H-imidazol-1-yl)ethylidene)bis-, disodium salt, tetrahydrate
|
| Synonyms |
Sodium (1-hydroxy-2-(1H-imidazol-1-yl)-1-Phosphonoethyl)phosphonate tetrahydrate; Zoledronic Acid, Disodium Salt, Tetrahydrate; Phosphonic acid, P,P'-[1-hydroxy-2-(1H-imidazol-1-yl)ethylidene]bis-, sodium salt, hydrate (1:2:4); disodium;(1-hydroxy-2-imidazol-1-yl-1-phosphonatoethyl)phosphonic acid;tetrahydrate; DISODIUM TETRAHYDRATE 1-HYDROXY-2-(IMIDAZOL-1-YL)-1-PHOSPHONOETHYLPHOSPHONATE; Sodium(1-hydroxy-2-(1H-imidazol-1-yl)-1-Phosphonoethyl)phosphonatetetrahydrate
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5766 mL | 12.8829 mL | 25.7659 mL | |
| 5 mM | 0.5153 mL | 2.5766 mL | 5.1532 mL | |
| 10 mM | 0.2577 mL | 1.2883 mL | 2.5766 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
