Zoledronic acid (ZOL 446)

Catalog No.S1314 Synonyms: Zoledronate, CGP-4244, GP42446A, Zometa, Zomera, Aclasta, Reclast

For research use only.

Zoledronic acid (ZOL 446, ZA, Zoledronate, CGP-4244, GP42446A, Zometa, Zomera, Aclasta, Reclast), 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. Zoledronic acid (ZA) also induces autophagy.

Zoledronic acid (ZOL 446) Chemical Structure

CAS No. 118072-93-8

Selleck's Zoledronic acid (ZOL 446) has been cited by 36 publications

Purity & Quality Control

Choose Selective Ras Inhibitors

Biological Activity

Description Zoledronic acid (ZOL 446, ZA, Zoledronate, CGP-4244, GP42446A, Zometa, Zomera, Aclasta, Reclast), 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. Zoledronic acid (ZA) also induces autophagy.
Targets
Rho [1]
(Cell-free assay)
Ras [1]
()
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 NCI-H460 cell MWjQdo9tcW[ncnH0bY9vKGG|c3H5 MXnBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKE6FST3IOFYxKGOnbHygcIlv\SCkeTDNWHQh[XO|YYmsJGlEPTB;MUGuO{DPxE1? MYG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yPjl5MESwOUc,OTZ7N{C0NFU9N2F-
human SF-268 cell NYfGVZVCWHKxbHnm[ZJifGmxbjDhd5NigQ>? NV\wXpBvSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDTSk0zPjhiY3XscEBtcW6nIHL5JG1VXCCjc4PhfUwhUUN3ME2xOE4{KM7:TR?= NVLrVJVERGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMU[5O|A1ODVpPkG2PVcxPDB3PD;hQi=>
Gamma delta T cells NWD6WWxzTnWwY4Tpc44h[XO|YYm= MkXwSYZn\WO2aY\lJINwdmOnboTyZZRqd25iYXfhbY5{fCCqdX3hckBI[W2vYTDk[Yx1[SCWIHPlcIx{NCCHQ{WwQVUvPM7:TR?= NVn5WoFnRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUW4Nlg5OzRpPkG1PFI5QDN2PD;hQi=>
HFF cells MmfLSpVv[3Srb36gZZN{[Xl? MkfiTY4hfmm2cn:gbY5pcWKrdH;yfUBkd26lZX70doF1cW:wIHHnZYlve3RidHjlJIdzd3e2aDDv[kBVd3ixcHzhd41iKGexbnTpbUBqdiCqdX3hckBnd3Knc3vpckBncWK{b3LsZZN1KG2xbn;sZZlmeiClZXzsd{ApUE[IIHPlcIx{MSxiSVO1NF0xNjd7zszN NVX3Rm9XRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUW4OVcyOTlpPkG1PFU4OTF7PD;hQi=>
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BL21(DE3) Mm\5SpVv[3Srb36gZZN{[Xl? MlTvN|AhdWmwcx?= MY\Jcohq[mm2aX;uJI9nKEirc{[teIFo\2WmIHj1cYFvKHS{dX7jZZRm\CCIUGDTJEg3NTN3Mzmg[ZhxemW|c3XkJIlvKEW|Y3jldolkcGmjIHPvcIkhSkx{MTjESVMqKGOnbHzzJJV{cW6pIHfldoFvgWxiZHnwbI9{eGijdHWgZY5lKGm|b4DlcpRmdnmuIHTpdIhwe3CqYYTlJIF{KHO3YoP0doF1\SCycnXpcoN2[mG2ZXSge4l1cCCnbor5cYUh\m:{IEOwJI1qdnNiYomgd5Bm[3S{b4Doc5RwdWW2cnnjJIFv[Wy7c3nzMEBKSzVyPUCuNe69VQ>? NETXPGY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{[xNFU6Pyd-MkO2NVA2QTd:L3G+
BL2-codon plus (DE3) RIL MmDjSpVv[3Srb36gZZN{[Xl? NIrkZ4I{OCCvaX7z MYHJcohq[mm2aX;uJI9nKE5vdHXycYlv[WxiSHnzOk11[WepZXSgVIxie22xZHn1cUB3cX[jeDDHS3BRWyCneIDy[ZN{\WRiaX6gSZNkcGW{aXPobYEh[2:uaTDCUFIu[2:mb36gdIx2eyBqRFWzLUBTUUxiY3XscJMhfXOrbneg[4Vz[W67bDDkbZBpd3OyaHH0[UBidmRiaYPvdIVvfGWweXyg[IlxcG:|cHjheIUh[XNic4Xid5Rz[XSnIIDy[Ylv[3WkYYTl[EB4cXSqIHXufplu\SCob4KgN|AhdWmwczDifUB{eGWldILvdIhwfG:vZYTybYMh[W6jbInzbZMtKEmFNUC9NE4yO87:TR?= MofqQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN4MUC1PVcoRjJ|NkGwOVk4RC:jPh?=
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C57BL mouse bone marrow cells NWPmPI5PTnWwY4Tpc44h[XO|YYm= NFLld282OCCwTR?= MnHCNVAhfG9iMUWg[IF6ew>? NUXIWWtWUW6mdXP0bY9vKG:oIH3pcoVz[WyrenH0bY9vKGmwIFO1O2JNKG2xdYPlJIJwdmVibXHydo94KGOnbHzzJIF1KDVyIH7NJJN2eHCuZX3lcpRm\CC5aYToJIZz\XOqIH3l[Il2dSClb370ZYlvcW6pIHPvcZBwfW6mIHX2[ZJ6KDNiZHH5d{Bnd3JiMUCgeI8hOTViZHH5d{BjgSCjbHn6ZZJqdiC{ZXSg[JlmKGKjc3XkJIF{e2G7 NIPIbHA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9|MEKxOlg2OSd-M{CyNVY5PTF:L3G+
C57BL mouse bone marrow cells/human PC3 cells MVvGeY5kfGmxbjDhd5NigQ>? NVnteVhOPTBidH:gNVAxKG6P NFvrb2gyOCC2bzCxOUBl[Xm| MUjJcoR2[3Srb36gc4YhdWmwZYLhcIl7[XSrb36gbY4hSzV5QlygcY92e2ViYn;u[UBu[XK{b4egZ4VtdHNiY3:tZ5VtfHW{ZXSge4l1cCCqdX3hckBRSzNiY3XscJMh[XRiNUCgeI8hOTByIH7NJJN2eHCuZX3lcpRm\CC5aYToJIZz\XOqIH3l[Il2dSClb370ZYlvcW6pIHPvcZBwfW6mIHX2[ZJ6KDNiZHH5d{Bnd3JiMUCgeI8hOTViZHH5d{BjgSCjbHn6ZZJqdiC{ZXSg[JlmKGKjc3XkJIF{e2G7 M2PKNFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzNyMkG2PFUyLz5|MEKxOlg2OTxxYU6=
K562 M3z2dWZ2dmO2aX;uJIF{e2G7 MkLWNlQxKG2rboO= MYHBZ5RqfmG2aX;uJI9nKGK3dInyc5BpcWyrbjCzRVEhcW5iaIXtZY4hUzV4MjDj[YxteyCjc4Pld5Nm\CCjczDpcpRmem[ncn;uMYdidW2jIIDyc4R2[3Srb36gdJJmfHKnYYTl[EBnd3JiMkSwJI1qdnNiZn;scI94\WRiYomgTG1DWFBvdILlZZRm\CCYZ3HtcYE6XmSnbIThNkBVKGOnbHzzJIFl\Gm2aX;uJIFv\CCvZXHzeZJm\CCjZoTldkAzOCCqcoOgZpkhTUyLU1GsJGVEPTB;MkROwG0> NIPuS|k9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9|MUWzNVE6QCd-M{G1N|EyQTh:L3G+
MIAPaCa2 MXXDfZRwfG:6aXPpeJkh[XO|YYm= NUW1UIVvPzJiaILz MmK2R5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gUWlCWGGFYUKgZ4VtdHNiYYPz[ZN{\WRiYYOg[IVkemWjc3WgbY4h[2WubDDndo94fGhibXXhd5Vz\WRiYX\0[ZIhPzJiaILzJIJ6KE2WVDDhd5NigSxiRVO1NF0yOy52zszN MkjmQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOzF5MkWyPVcoRjNzN{K1Nlk4RC:jPh?=
PANC1 MV3DfZRwfG:6aXPpeJkh[XO|YYm= M3rJelczKGi{cx?= NHW4cnFEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBRSU6FMTDj[YxteyCjc4Pld5Nm\CCjczDk[YNz\WG|ZTDpckBk\WyuIHfyc5d1cCCvZXHzeZJm\CCjZoTldkA4OiCqcoOgZpkhVVSWIHHzd4F6NCCHQ{WwQVE3NjIQvF2= NHjLVWs9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9|MUeyOVI6Pyd-M{G3NlUzQTd:L3G+
Assay
Methods Test Index PMID
Western blot ALDH1 / Oct4 / Nanog / Sox2 / CD49f ; N-cadherin / E-cadherin / Vimentin 30791957
Growth inhibition assay Cell viability 30791957
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 (from reference)

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

Chemical Information

Molecular Weight 272.09
Formula

C5H10N2O7P2

CAS No. 118072-93-8
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles C1=CN(C=N1)CC(O)(P(=O)(O)O)P(=O)(O)O

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT05080790 Recruiting Drug: Dinutuximab Beta Zoledronic acid Interleukin-2 Leiomyosarcoma Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest|EUSA Pharma Inc. November 15 2021 Phase 2
NCT04719481 Not yet recruiting Drug: Pravastatin Sodium 80 MG|Drug: Placebo Postmenopausal Osteoporosis Peking University Third Hospital November 2021 Phase 4
NCT04719650 Not yet recruiting Drug: Zoledronic Acid Injection|Drug: Placebo Postmenopausal Osteoporosis Peking University Third Hospital October 2021 Phase 4
NCT04034199 Unknown status Drug: Denosumab|Drug: Zoledronic Acid Idiopathic Inflammatory Myopathies|Osteoporosis Osteopenia Kwong Wah Hospital|Tung Wah Group of Hospitals August 15 2019 Phase 3
NCT03862833 Recruiting Drug: IL2|Drug: Zoledronic Acid Hematopoietic Stem Cell Transplantation Nantes University Hospital May 7 2019 Phase 1

(data from https://clinicaltrials.gov, updated on 2022-01-17)

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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Frequently Asked Questions

Question 1:
How can I reconstitute the compound for in vivo studies?

Answer:
Please dissolve this compound directly to 30% PEG400+0.5% Tween80+5% Propylene glycol.

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