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| 100mg |
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| 250mg |
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| 500mg |
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| 1g |
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Zoledronic acid hydrate (Zoledronate; CGP 42446; CGP42446A; ZOL 446) is potent and semisynthetic bisphosphonate with anti-bone-resorption activity. It induces apoptosis in osteoclasts by inhibiting enzymes of the mevalonate pathway and preventing the isoprenylation of small GTP-binding proteins such as Ras and Rho. Zoledronic acid is a synthetic imidazole bisphosphonate analog of pyrophosphate with anti-bone-resorption activity. As a third-generation bisphosphonate, zoledronic acid binds to hydroxyapatite crystals in the bone matrix, slowing their dissolution and inhibiting the formation and aggregation of these crystals.
| ln Vitro |
In osteocyte-like MLO-Y4 cells, zoledronic acid monohydrate (0.1–1 µM; 48 hours) enhances the expression of sclerostin and receptor activator of nuclear factor kB ligand (RANKL) mRNA[2]. The expression of osteoclastogenesis supporting factor from MLO-Y4 cells is increased by zoledronic acid monohydrate[2]. In MLO-Y4 cells, zoledronic acid monohydrate increases the production of RANKL through the IL-6/JAK2/STAT3 pathway[2]. Monohydrate zoledronic acid suppresses osteoclast development and function by modulating the JNK and NF-κB signaling pathways[3]. In MC3T3-E1 cells, zoledronic acid monohydrate (10-100 µM; 1-7 days) significantly lowers viability[4]. In MC3T3-E1 cells, zoledronic acid monohydrate (10-100 µM; 1-7 days) causes apoptosis[4]. Because it induces apoptosis, zoledronic acid monohydrate (10–100 µM; 4 days) reduces cell viability[4]. At concentrations less than 1 µM, zoledronic acid monohydrate inhibits the differentiation and maturation of MC3T3-E1 cells[4].
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| ln Vivo |
For three weeks, zoledronic acid monohydrate (0.05 mg/kg; intraperitoneally; weekly) enhances the density and content of bone mineral[5]. In vivo bone remodeling and osteoclast and osteoblast function are inhibited by zoledronic acid monohydrate (0.5–1 mg/kg; i.p.; weekly; for 3 weeks), which interferes with the mechanical characteristics of bone[5].
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| Cell Assay |
Cell Viability Assay[4]
Cell Types: MC3T3-E1 cells Tested Concentrations: 0.02 µM, 0.1 µM, 1 µM, 10 µM, 100 µM Incubation Duration: 1 day, 3 days, 5 days, 7 days Experimental Results: decreased cells viability at 10 µM and 100 µM. Apoptosis Analysis[4] Cell Types: MC3T3-E1 cells Tested Concentrations: 0.02 µM, 0.1 µM, 1 µM, 10 µM, 100 µM Incubation Duration: 1 days, 4 days, 7 days Experimental Results: Increased the number of early apoptotic cells and late apoptotic or necrotic cells at dose-dependent and time-dependent (high concentrations). Western Blot Analysis[4] Cell Types: MC3T3-E1 cells Tested Concentrations: 0.02 µM, 0.1 µM, 1 µM, 10 µM, 100 µM Incubation Duration: 4 days Experimental Results: Down-regulated the protein level of inactive caspase-3 and up-regulated the protein level of active caspase-3 at the concentrations of 10 and 100 µM. |
| 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, weekly, for 3 weeks Experimental Results: Inhibited both osteoclast and osteoblasts function and bone remodeling at 0.5 mg/kg and 1 mg/kg. |
| References |
[1]. Lianwei Wang, et al. Various pathways of zoledronic acid against osteoclasts and bone cancer metastasis: a brief review. BMC Cancer. 2020; 20: 1059.
[2]. Hyung Joon Kim, et al. Zoledronate Enhances Osteocyte-Mediated Osteoclast Differentiation by IL-6/RANKL Axis. Int J Mol Sci. 2019 Mar; 20(6): 1467. [3]. Xiao-Lin Huang, et al. Zoledronic acid inhibits osteoclast differentiation and function through the regulation of NF-κB and JNK signalling pathways. Int J Mol Med. 2019 Aug;44(2):582-592. [4]. XIN HUANG, et al. Dose-dependent inhibitory effects of zoledronic acid on osteoblast viability and function in vitro. Mol Med Rep. 2016 Jan; 13(1): 613-622. [5]. Samantha Pozzi, et al. High-dose zoledronic acid impacts bone remodeling with effects on osteoblastic lineage and bone mechanical properties. Clin Cancer Res. 2009 Sep 15;15(18):5829-39. [6]. Shea GKH, et al. Oral Zoledronic acid bisphosphonate for the treatment of chronic low back pain with associated Modic changes: A pilot randomized controlled trial. J Orthop Res. 2022 Feb 23. |
| Molecular Formula |
C5H12N2O8P2
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|---|---|
| Molecular Weight |
290.1
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| Exact Mass |
271.99632
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| CAS # |
165800-06-6
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| Related CAS # |
Zoledronic Acid;118072-93-8;Zoledronic acid disodium tetrahydrate;165800-07-7
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| SMILES |
OC(P(O)(O)=O)(P(O)(O)=O)CN1C=CN=C1.[H]O[H]
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| InChi Key |
FUXFIVRTGHOMSO-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C5H10N2O7P2.H2O/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);1H2
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| Chemical Name |
(1-hydroxy-2-(1H-imidazol-1-yl)ethane-1,1-diyl)diphosphonic acid hydrate
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| Synonyms |
CGP42446; CGP42446A; ZOL446; CGP-42446; CGP-42446A; ZOL-446; CGP 42446; CGP 42446A; ZOL 446; Zoledronate, trade names: Zometa; Reclast.
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| 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)
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| Solubility (In Vitro) |
H2O : ~14.29 mg/mL (~49.26 mM)
DMSO :< 1 mg/mL |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 3.33 mg/mL (11.48 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication (<60°C).
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.4471 mL | 17.2354 mL | 34.4709 mL | |
| 5 mM | 0.6894 mL | 3.4471 mL | 6.8942 mL | |
| 10 mM | 0.3447 mL | 1.7235 mL | 3.4471 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.
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