Zoledronic Acid

Catalog No.S1314 Synonyms: Zoledronate, CGP-4244

Zoledronic Acid  Chemical Structure

Molecular Weight(MW): 272.09

Zoledronic acid (ZA), a potent osteoclast inhibitor, 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.

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2 Customer Reviews

  • Quantification (C) of SA-β-gal+ SMCs after sustained 100nM ADP treatment for 48hr with or without Ras inhibitor zoledronic acid (ZA) (n=4 in each group). #p<0.05, ##p<0.01 compared with control, *p<0.05 compared with P2ry12+/+ADP. (D) Incidence of TAAD formation and rupture after BAPN administration with or without ZA. (E) Elastin degradation grades of mice aortas after BAPN administration with or without ZA. (F) Representative H&E staining of thoracic aorta and progression of thoracic aorta diameter of mice aortas after BAPN administration with or without ZA (n=8 in both group). (G) Representative images and quantification of SA-β-gal (blue) staining in mouse aorta after BAPN administration with or without ZA (n=4 in both group); arrow, location of SA-β-gal+ area. (H) Immunostaining and quantification of p-ERK and p-p38 in mouse aorta with or without ZA (n=4 in both group). Data are meanSD from three experiments.*p<0.05, compared with no ZA.

    J Mol Cell Cardiol, 2016, 99:76-86.. Zoledronic Acid purchased from Selleck.

    Isolation of cd T cells. PBMCs were cultured in the presence of 400 nM ZA and 200 IU/ml IL-2 over 10 days. cd T cells were isolated by negative MACS isolation. Flow cytometric analysis revealed co-expression of CD3 and TCRcd on over 99% of cells of the flow through fraction (A). The T cells expressed the TCRVd2 chain (B) and the CD56 protein (C).

    Liver Int 2013 33(1), 127-36. Zoledronic Acid purchased from Selleck.

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Biological Activity

Description Zoledronic acid (ZA), a potent osteoclast inhibitor, 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.
Targets
Rho [1]
(Cell-free assay)
In vitro

Zoledronic acid (10 µM and 100 µM) causes a significant reduction in the proportions of MCF-7 cells (49.54% and 23.55% of control, respectively) (P < 0.05). Zoledronic acid has little effect on MDA-MB-231 cells at concentrations of 0.1–10 µM, whereas the 100 µM concentration results in a significant reduction in cell number. Zoledronic acid (100 µM) results in a 63.5% reduction in MCF-7 cell number at 72 hours and an 87.1% reduction at 96 hours. Zoledronic acid (10 µM) results in a greater than 4-fold increase in MCF-7 cell apoptosis whereas the 100 µM concentration induces a 6-fold increase in the proportion of apoptotic cells. Zoledronic acid (10 µM) and paclitaxel (2 µM) results in a 5-fold increase in apoptosis (774.8% of control) compared to zoledronic acid alone (155.71%) and a 4-fold increase compared to paclitaxel alone (189.68%). Zoledronic acid-induced apoptosis of MCF-7 breast cancer cells can be inhibited by addition of intermediates of the mevalonate pathway, which is consistent with observations in osteoclasts, macrophages and myeloma cells. [1] Zoledronic acid enhances OPG gene expression and protein secretion by human osteoblasts (hOB) in a dose-dependent fashion with a maximum effect at 10 nM after 72 hours, consistent with the higher biological potency of Zoledronic acid. Zoledronic acid prevents the inhibitory effects of the glucocorticoid dexamethasone on OPG mRNA and protein production in human osteoblasts. Zoledronic acid induces type I collagen secretion and alkaline phosphatase activity by 2- and 4-fold, respectively, in human osteoblasts. [2]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
human foreskin fibroblast monolayer cells (HFF cells) NHPNN2RIem:5dHigbY5pcWKrdHnvckBie3OjeR?= MnLnTY4hfmm2cn:gbY5pcWKrdH;yfUBkd26lZX70doF1cW:wIHHnZYlve3RidHjlJIdzd3e2aDDv[kBVd3ixcHzhd41iKGexbnTpbUBqdiCqdX3hckBnd3Knc3vpckBncWK{b3LsZZN1KG2xbn;sZZlmeiClZXzsd{ApUE[IIHPlcIx{MSxiSVO1NF0xNjd7IN88US=> MXOxOVg2PzFzOR?=
human Gamma delta T cells M1TMZWZ2dmO2aX;uJIF{e2G7 MYrF[oZm[3SrdnWgZ49v[2WwdILheIlwdiCjZ3HpcpN1KGi3bXHuJGdidW2jIHTlcJRiKFRiY3XscJMtKEWFNUC9OU41KM7:TR?= MknDNVU5Ojh6M{S=
mouse J774 cells MlHwR5l1d3SxeHnjxsBie3OjeR?= MoXXR5l1d3SxeHnjbZR6KGGpYXnud5QhdW:3c3WgTlc4PCClZXzsd{Bie3Onc4Pl[EBieyC{ZXT1Z5Rqd25iaX6gZ4VtdCC4aXHibYxqfHluIFnDOVA:Py56IN88US=> M3\oSFI1QDF|N{Sy
human RPMI8226 cells M1PqfWN6fG:2b4jpZ:Kh[XO|YYm= MYe3NkBp NYjoVohES3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hWlCPSUiyNlYh[2WubIOgZYZ1\XJiN{KgbJJ{KGK7IF3UWEBie3OjeTygSWM2OD1zMTFOwG0> M3vSc|I{QTl6OUKx
human NCI-H460 cell NFTyXFhRem:uaX\ldoF1cW:wIHHzd4F6 M3PCOGFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iTlPJMWg1PjBiY3XscEBtcW6nIHL5JG1VXCCjc4PhfUwhUUN3ME2xNU44KM7:TR?= NVzOcWdzOTZ7N{C0NFU>
human SF-268 cell MVHQdo9tcW[ncnH0bY9vKGG|c3H5 M4rjN2FvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iU1[tNlY5KGOnbHygcIlv\SCkeTDNWHQh[XO|YYmsJGlEPTB;MUSuN{DPxE1? M37De|E3QTdyNEC1
human MCF7 cells Mn:4VJJwdGmoZYLheIlwdiCjc4PhfS=> NVrSWlY2PzJiaB?= MnzERY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDoeY1idiCPQ1[3JINmdGy|IHHmeIVzKDd{IHjyd{BjgSCPVGSgZZN{[XluIFnDOVA:OjNizszN MoWzNlQ6Ojh|OUm=

... Click to View More Cell Line Experimental Data

In vivo Zoledronic acid (120 mg/kg, s.c.) prevents the formation of lesions, prevents cancellous bone loss and loss of bone mineral density, and reduces osteoclast perimeter in 5T2MM-bearing mice. Zoledronic acid (120 mg/kg, s.c.) also decreases paraprotein concentration, decreases tumor burden, and reduces angiogenesis in 5T2MM-bearing mice. [3]

Protocol

Solubility (25°C)

In vitro 0.1M NaOH (aq) 40 mg/mL (147.01 mM)
DMSO 0.004 mg/mL (0.01 mM)
Water Insoluble
In vivo Add solvents individually and in order:
30% PEG400+0.5% Tween80+5% Propylene glycol
10mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 272.09
Formula

C5H10N2O7P2

CAS No. 118072-93-8
Storage powder
Synonyms Zoledronate, CGP-4244

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Clinical Trial Information

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT02632903 Not yet recruiting Osteoporosis|Osteonecrosis|Acute Lymphoblastic Leukemia Childrens Hospital of Eastern Ontario October 2016 Phase 2
NCT02721433 Recruiting Breast Cancer|Prostate Cancer|Metastasis Ottawa Hospital Research Institute August 2016 Phase 4
NCT02632916 Recruiting Osteoporosis Childrens Hospital of Eastern Ontario August 2016 Phase 2
NCT02480634 Not yet recruiting Non-small Cell Lung Cancer|Bone Metastasis Daping Hospital and the Research Institute of Surgery of the Third Military Medical University June 2016 Phase 4
NCT02508038 Recruiting Acute Myeloid Leukemia|Acute Lymphoblastic Leukemia|Hodgkin Lymphoma|Non-Hodgkin Lymphoma|Myelodysplastic Syndrome|Myeloproliferative Syndrome|Rhabdomyosarcoma|Ewing Sarcoma|Primitive Neuroectodermal Tumor|Osteosarcoma|Neuroblastoma University of Wisconsin, Madison January 2016 Phase 1
NCT02069340 Not yet recruiting Malignant Neoplasm|Musculoskeletal Complications University of Southern California|National Cancer Institute (NCI) January 2016 --

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Rho Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID