Synonym
Zoledronic acid; CGP 42446; CGP42446A; ZOL 446; zoledronate; zoledronate. brand name: Zometa; Reclast.
IUPAC/Chemical Name
(1-hydroxy-2-(1H-imidazol-1-yl)ethane-1,1-diyl)diphosphonic acid hydrate
InChi Key
FUXFIVRTGHOMSO-UHFFFAOYSA-N
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
SMILES Code
OC(P(O)(O)=O)(P(O)(O)=O)CN1C=CN=C1.[H]O[H]
Appearance
white solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
To be determined.
Shelf Life
>2 years if stored properly
Drug Formulation
To be determined.
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
Zoledronic acid monohydrate (Zoledronate monohydrate) is a third-generation bisphosphonate (BP), with potent anti-resorptive activity.
In vitro activity:
In the present paper this study shows that by using ZOL (Zoledronic acid) that inhibition of the mevalonate pathway at the stage of farnesylation (FDP synthase) compromises the growth of the CB-MA9 cells, particularly when the cells require membrane dependent cell-cell interactions in 3D colony culture. ZOL was also found to effectively inhibit the formation and size of cobblestone like structures which form when HSCs or MA9 cells migrate burrowing underneath the stromal layer.
Reference: Heliyon. 2020 Jun; 6(6): e04020. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7283156/
In vivo activity:
In the SKOV3ip1 mouse model, restraint stress increased tumor growth by 4.07-fold (mean difference 0.834 g) and nodule counts by 3.54-fold (mean difference 14.14), while ZA (Zoledronic acid) significantly abrogated this effect (Figure 5b; p < 0.001). In the HeyT30 model, stress significantly increased tumor growth by 2.0-fold (mean difference 1.769 g), and nodule counts by 2.5-fold (mean difference 4.5). Similarly to the SKOV3ip1 model, ZA treatment prevented the effects of stress on tumor growth and nodule development in the HeyT30 model (Figure 5c; p < 0.05).
Reference: Cancers (Basel). 2020 Sep; 12(9): 2671. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563308/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
0.0 |
0.03 |
| PBS (pH 7.2) |
1.6 |
5.52 |
| Water |
1.0 |
3.45 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
290.10
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Chiarella E, Codispoti B, Aloisio A, Cosentino EG, Scicchitano S, Montalcini Y, Lico D, Morrone G, Mesuraca M, Bond HM. Zoledronic acid inhibits the growth of leukemic MLL-AF9 transformed hematopoietic cells. Heliyon. 2020 Jun 5;6(6):e04020. doi: 10.1016/j.heliyon.2020.e04020. PMID: 32529062; PMCID: PMC7283156.
2. Huang XL, Huang LY, Cheng YT, Li F, Zhou Q, Wu C, Shi QH, Guan ZZ, Liao J, Hong W. 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. doi: 10.3892/ijmm.2019.4207. Epub 2019 May 23. PMID: 31173157; PMCID: PMC6605660.
3. Colon-Echevarria CB, Ortiz T, Maldonado L, Hidalgo-Vargas MJ, Pérez-Morales J, Aquino-Acevedo AN, Herrera-Noriega R, Bonilla-Claudio M, Castro EM, Armaiz-Pena GN. Zoledronic Acid Abrogates Restraint Stress-Induced Macrophage Infiltration, PDGF-AA Expression, and Ovarian Cancer Growth. Cancers (Basel). 2020 Sep 18;12(9):2671. doi: 10.3390/cancers12092671. PMID: 32962103; PMCID: PMC7563308.
4. Yang X, Xu X, Chen J, Wang Q, Wang G, Ai X, Wang X, Pan J. Zoledronic acid regulates the synthesis and secretion of IL-1β through Histone methylation in macrophages. Cell Death Discov. 2020 Jun 11;6:47. doi: 10.1038/s41420-020-0273-4. PMID: 32566254; PMCID: PMC7289826.
In vitro protocol:
1. Chiarella E, Codispoti B, Aloisio A, Cosentino EG, Scicchitano S, Montalcini Y, Lico D, Morrone G, Mesuraca M, Bond HM. Zoledronic acid inhibits the growth of leukemic MLL-AF9 transformed hematopoietic cells. Heliyon. 2020 Jun 5;6(6):e04020. doi: 10.1016/j.heliyon.2020.e04020. PMID: 32529062; PMCID: PMC7283156.
2. Huang XL, Huang LY, Cheng YT, Li F, Zhou Q, Wu C, Shi QH, Guan ZZ, Liao J, Hong W. 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. doi: 10.3892/ijmm.2019.4207. Epub 2019 May 23. PMID: 31173157; PMCID: PMC6605660.
In vivo protocol:
1. Colon-Echevarria CB, Ortiz T, Maldonado L, Hidalgo-Vargas MJ, Pérez-Morales J, Aquino-Acevedo AN, Herrera-Noriega R, Bonilla-Claudio M, Castro EM, Armaiz-Pena GN. Zoledronic Acid Abrogates Restraint Stress-Induced Macrophage Infiltration, PDGF-AA Expression, and Ovarian Cancer Growth. Cancers (Basel). 2020 Sep 18;12(9):2671. doi: 10.3390/cancers12092671. PMID: 32962103; PMCID: PMC7563308.
2. Yang X, Xu X, Chen J, Wang Q, Wang G, Ai X, Wang X, Pan J. Zoledronic acid regulates the synthesis and secretion of IL-1β through Histone methylation in macrophages. Cell Death Discov. 2020 Jun 11;6:47. doi: 10.1038/s41420-020-0273-4. PMID: 32566254; PMCID: PMC7289826.
1: Albani-Campanario M, BuendÃa-DÃaz G, Flores-Islas Mde L, Maquita-Nakano C, Ochoa-Cervantes J. [Zoledronic acid-based uveitis: a case report and a bibliography review]. Ginecol Obstet Mex. 2012 May;80(5):355-9. Review. Spanish. PubMed PMID: 23301428.
2: Huang WW, Huang C, Liu J, Zheng HY, Lin L. Zoledronic acid as an adjuvant therapy in patients with breast cancer: a systematic review and meta-analysis. PLoS One. 2012;7(7):e40783. doi: 10.1371/journal.pone.0040783. Epub 2012 Jul 26. Review. PubMed PMID: 22844410; PubMed Central PMCID: PMC3406041.
3: Zhang J, Wang R, Zhao YL, Sun XH, Zhao HX, Tan L, Chen DC, Hai-Bin X. Efficacy of intravenous zoledronic acid in the prevention and treatment of osteoporosis: a meta-analysis. Asian Pac J Trop Med. 2012 Sep;5(9):743-8. doi: 10.1016/S1995-7645(12)60118-7. Review. PubMed PMID: 22805729.
4: Hadji P, Coleman R, Gnant M, Green J. The impact of menopause on bone, zoledronic acid, and implications for breast cancer growth and metastasis. Ann Oncol. 2012 Nov;23(11):2782-90. doi: 10.1093/annonc/mds169. Epub 2012 Jun 22. Review. PubMed PMID: 22730099; PubMed Central PMCID: PMC3477882.
5: Carter JA, Botteman MF. Health-economic review of zoledronic acid for the management of skeletal-related events in bone-metastatic prostate cancer. Expert Rev Pharmacoecon Outcomes Res. 2012 Aug;12(4):425-37. doi: 10.1586/erp.12.31. Epub 2012 Apr 27. Review. PubMed PMID: 22540167.
6: Dranitsaris G, Hatzimichael E. Interpreting results from oncology clinical trials: a comparison of denosumab to zoledronic acid for the prevention of skeletal-related events in cancer patients. Support Care Cancer. 2012 Jul;20(7):1353-60. doi: 10.1007/s00520-012-1461-4. Epub 2012 Apr 27. Review. PubMed PMID: 22539050; PubMed Central PMCID: PMC3360851.
7: Gnant M. Zoledronic acid in the treatment of early-stage breast cancer: is there a final verdict? Curr Oncol Rep. 2012 Feb;14(1):35-43. doi: 10.1007/s11912-011-0209-5. Review. PubMed PMID: 22113793.
8: Yan T, Yin W, Zhou Q, Zhou L, Jiang Y, Du Y, Shao Z, Lu J. The efficacy of zoledronic acid in breast cancer adjuvant therapy: a meta-analysis of randomised controlled trials. Eur J Cancer. 2012 Jan;48(2):187-95. doi: 10.1016/j.ejca.2011.10.021. Epub 2011 Nov 17. Review. PubMed PMID: 22100904.
9: Hamilton E, Clay TM, Blackwell KL. New perspectives on zoledronic acid in breast cancer: potential augmentation of anticancer immune response. Cancer Invest. 2011 Oct;29(8):533-41. doi: 10.3109/07357907.2011.605413. Epub 2011 Aug 15. Review. PubMed PMID: 21843051.
10: Lipton A. Zoledronic acid: multiplicity of use across the cancer continuum. Expert Rev Anticancer Ther. 2011 Jul;11(7):999-1012. doi: 10.1586/era.11.71. Review. PubMed PMID: 21806323.
1. Jayaram R, O'Donnell PW, Puleo DA. Systems for local, sustained release of zoledronic acid as a potential treatment for metastatic bone disease. Mater Sci Eng C Mater Biol Appl. 2021 Jan;118:111395. doi: 10.1016/j.msec.2020.111395. Epub 2020 Aug 22. PMID: 33255000.
2. Pandey GK, Landman N, Neikes HK, Hulsman D, Lieftink C, Beijersbergen R, Kolluri KK, Janes SM, Vermeulen M, Badhai J, van Lohuizen M. Genetic screens reveal new targetable vulnerabilities in BAP1-deficient mesothelioma. Cell Rep Med. 2023 Jan 10:100915. doi: 10.1016/j.xcrm.2022.100915. Epub ahead of print. PMID: 36657447.
