Home Apoptosis Apoptosis related inducer Zoledronic acid (Zoledronate)

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Zoledronic acid (Zoledronate) Bone Resorption Inhibitor

N. Cat.: S1314

Zoledronic acid (Zoledronate), 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 (Zoledronate) Apoptosis related inducer Chemical Structure

Struttura chimica

Peso molecolare: 272.09

Vai a

Controllo Qualità (Quality Control)

Lotto: Purezza: 99.80%
99.80

Coltura cellulare, trattamento e concentrazione di lavoro
(Cell Culture, Treatment & Working Concentration)

Linee cellulari Tipo di saggio Concentrazione Tempo di incubazione Formulazione Descrizione dell'attività PMID
human NCI-H460 cell Proliferation assay Antiproliferative activity against human NCI-H460 cell line by MTT assay, IC50=11.7 μM 16970405
human SF-268 cell Proliferation assay Antiproliferative activity against human SF-268 cell line by MTT assay, IC50=14.3 μM 16970405
Gamma delta T cells Function assay Effective concentration against human Gamma delta T cells, EC50=5.4μM 15828834
HFF cells Function assay In vitro inhibitory concentration against the growth of Toxoplasma gondii in human foreskin fibroblast monolayer cells (HFF cells), IC50=0.79μM 15857119
HFF cells Function assay Inhibitory concentration against the growth of Toxoplasma gondii overexpressing FPPS enzyme in human foreskin fibroblast monolayer cells; (control = 0.60 uM, experiment 1), IC50=7.8μM 15857119
HFF cells Function assay Inhibitory concentration against the growth of Toxoplasma gondii overexpressing FPPS enzyme in human foreskin fibroblast monolayer cells; (control = 0.79 uM, experiment 3), IC50=7.8μM 15857119
HFF cells Function assay Inhibitory concentration against the growth of Toxoplasma gondii overexpressing FPPS enzyme in human foreskin fibroblast monolayer cells; (control = 1.1 uM, experiment 2), IC50=8.3μM 15857119
BT-549 Antitumor assay Antitumor activity against human BT-549 cells xenografted SCID mouse co-transfected with human gamma delta T lymphocytes assessed as survival time prolongation at 2 ug, ip coadministered with human recombinant IL2 18937434
BT-549 Antitumor assay Antitumor activity against human BT-549 cells xenografted SCID mouse co-transfected with human gamma delta T lymphocytes assessed as survival time prolongation at 5 ug, ip coadministered with human recombinant IL2 18937434
BL21(DE3) Function assay 30 mins Inhibition of His6-tagged human truncated FPPS (6-353) expressed in Escherichia coli BL21(DE3) cells using geranyl diphosphate and isopentenyl diphosphate as substrate preincubated with enzyme for 30 mins by spectrophotometric analysis, IC50=0.1μM 23610597
BL2-codon plus (DE3) RIL Function assay 30 mins Inhibition of N-terminal His6-tagged Plasmodium vivax GGPPS expressed in Escherichia coli BL2-codon plus (DE3) RIL cells using geranyl diphosphate and isopentenyl diphosphate as substrate preincubated with enzyme for 30 mins by spectrophotometric analysis, IC50=0.13μM 23610597
RPMI8226 Cytotoxicity assay 72 hrs Cytotoxicity against human RPMI8226 cells after 72 hrs by MTT assay, EC50=11μM 23998921
J774 Cytotoxicity assay Cytotoxicity against mouse J774 cells assessed as reduction in cell viability, IC50=7.8μM 24813742
MCF7 Antiproliferative assay 72 hrs Antiproliferative activity against human MCF7 cells after 72 hrs by MTT assay, IC50=23μM 24928399
Vgamma9/Vdelta2 T-cells Function assay 18 hrs Binding affinity to butyrophilin 3A1 in human Vgamma9/Vdelta2 T-cells assessed as activation of Vgamma9/Vdelta2 T-cells by upregulation of CD69 and CD25 after 18 hrs, EC50=0.4866μM 29457898
RPMI8226 Antiproliferative assay 72 hrs Antiproliferative activity against human RPMI8226 cells after 72 hrs by MTT assay, EC50=11μM 30016091
RPMI8226 Function assay 0.5 uM Inhibition of GGPPS in human RPMI8226 cells assessed as reduction in Rap1A prenylation at 0.5 uM by Western blot analysis 30016091
J774A.1 Antiproliferative assay 100 uM 72 hrs Antiproliferative activity against mouse J774A.1 cells assessed as reduction in cell viability at 100 uM after 72 hrs by WST8 assay 30216851
RAW264.7 Antiproliferative assay 100 uM 72 hrs Antiproliferative activity against mouse RAW264.7 cells assessed as reduction in cell viability at 100 uM after 72 hrs by WST8 assay 30216851
MG63 Antiproliferative assay 100 uM 72 hrs Antiproliferative activity against human MG63 cells assessed as reduction in cell viability at 100 uM after 72 hrs by WST8 assay 30216851
PC3 Antiproliferative assay 100 uM 72 hrs Antiproliferative activity against human PC3 cells assessed as reduction in cell viability at 100 uM after 72 hrs by WST8 assay 30216851
RAW264.7 Antiproliferative assay 100 uM 72 hrs Antiproliferative activity against RANKL-differentiated mouse RAW264.7 cells assessed as reduction in cell viability at 100 uM after 72 hrs by CCK8 assay 30216851
RAW264.7 Function assay 72 hrs Inhibition of RANKL-induced osteoclastogenesis in mouse RAW264.7 cells after 72 hrs by TRAP staining based microscopic analysis 30216851
MC3T3-E1 Function assay 30 to 50 nM 10 to 15 days Induction of mineralization in mouse MC3T3-E1 cells at 30 to 50 nM after 10 to 15 days by alizarin red dye based assay 30216851
C57BL mouse bone marrow cells Function assay 50 nM 10 to 15 days Induction of mineralization in C57BL mouse bone marrow cells at 50 nM supplemented with fresh medium containing compound every 3 days for 10 to 15 days by alizarin red dye based assay 30216851
C57BL mouse bone marrow cells/human PC3 cells Function assay 50 to 100 nM 10 to 15 days Induction of mineralization in C57BL mouse bone marrow cells co-cultured with human PC3 cells at 50 to 100 nM supplemented with fresh medium containing compound every 3 days for 10 to 15 days by alizarin red dye based assay 30216851
K562 Function assay 240 mins Activation of butyrophilin 3A1 in human K562 cells assessed as interferon-gamma production pretreated for 240 mins followed by HMBPP-treated Vgamma9Vdelta2 T cells addition and measured after 20 hrs by ELISA, EC50=23μM 31531198
MIAPaCa2 Cytotoxicity assay 72 hrs Cytotoxicity against human MIAPaCa2 cells assessed as decrease in cell growth measured after 72 hrs by MTT assay, EC50=13.4μM 31725297
PANC1 Cytotoxicity assay 72 hrs Cytotoxicity against human PANC1 cells assessed as decrease in cell growth measured after 72 hrs by MTT assay, EC50=16.1μM 31725297
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Informazioni chimiche, conservazione e stabilità (Chemical Information, Storage & Stability)

Peso molecolare 272.09 Formula

C5H10N2O7P2

 Conservazione (Dalla data di ricezione)
N. CAS 118072-93-8 Scarica SDF Conservazione delle soluzioni stock

Sinonimi ZA, CGP-4244, GP42446A, ZOL 446 Smiles C1=CN(C=N1)CC(O)(P(=O)(O)O)P(=O)(O)O

Solubilità (Solubility)

In vitro
Lotto:

0.1M NAOH : 25 mg/mL (Ultrasonic and heating for 5 minutes.)

Water : 0.5 mg/mL (Warmed with 50℃ water bath; Ultrasonicated)

DMSO : Insoluble
(Il DMSO contaminato da umidità può ridurre la solubilità. Utilizzare DMSO fresco e anidro.)

Calcolatore di Molarità

Massa Concentrazione Volume Peso molecolare
Calcolatore di Diluizione Calcolatore del Peso Molecolare

In vivo
Lotto:

Calcolatore di formulazione in vivo (Soluzione chiara)

Passo 1: Inserire le informazioni di seguito (Consigliato: Un animale aggiuntivo per tenere conto della perdita durante l'esperimento)

mg/kg g μL

Passo 2: Inserire la formulazione in vivo (Questo è solo il calcolatore, non la formulazione. Contattateci prima se non c'è una formulazione in vivo nella sezione Solubilità.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Risultati del calcolo:

Concentrazione di lavoro: mg/ml;

Metodo per preparare il liquido master di DMSO: mg farmaco predissolto in μL DMSO ( Concentrazione del liquido master mg/mL, Vi preghiamo di contattarci prima se la concentrazione supera la solubilità del DMSO del lotto del farmaco. )

Metodo per preparare la formulazione in vivo: Prendere μL DMSO liquido master, quindi aggiungereμL PEG300, mescolare e chiarire, quindi aggiungereμL Tween 80, mescolare e chiarire, quindi aggiungere μL ddH2O, mescolare e chiarire.

Metodo per preparare la formulazione in vivo: Prendere μL DMSO liquido master, quindi aggiungere μL Olio di mais, mescolare e chiarire.

Nota: 1. Si prega di assicurarsi che il liquido sia limpido prima di aggiungere il solvente successivo.
2. Assicurarsi di aggiungere il/i solvente/i in ordine. È necessario assicurarsi che la soluzione ottenuta, nell'aggiunta precedente, sia una soluzione limpida prima di procedere all'aggiunta del solvente successivo. Metodi fisici come il vortex, gli ultrasuoni o il bagno d'acqua calda possono essere utilizzati per facilitare la dissoluzione.

Meccanismo d'azione (Mechanism of Action)

Targets/IC50/Ki
Rho
(Cell-free assay)
Ras
In vitro

Zoledronic acid (Zoledronate) (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). It 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. This compound (100 µM) results in a 63.5% reduction in MCF-7 cell number at 72 hours and an 87.1% reduction at 96 hours. It (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. When combined with paclitaxel (2 µM), it (10 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%). Its 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.

It 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. This compound prevents the inhibitory effects of the glucocorticoid dexamethasone on OPG mRNA and protein production in human osteoblasts. It induces type I collagen secretion and alkaline phosphatase activity by 2- and 4-fold, respectively, in human osteoblasts.

In vivo

Zoledronic acid (Zoledronate) (120 ug/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. It (120 mg/kg, s.c.) also decreases paraprotein concentration, decreases tumor burden, and reduces angiogenesis in 5T2MM-bearing mice.

Riferimenti

Applicazioni (Applications)

Metodi Biomarcatori Immagini PMID
Western blot ALDH1 / Oct4 / Nanog / Sox2 / CD49f N-cadherin / E-cadherin / Vimentin
S1314-WB1
30791957
Growth inhibition assay Cell viability
S1314-viability1
30791957

Informazioni sullo studio clinico (Clinical Trial Information)

(dati da https://clinicaltrials.gov, aggiornato il 2024-05-22)

Numero NCT Reclutamento Condizioni Sponsor/Collaboratori Data di inizio Fasi
NCT06217718 Not yet recruiting
Copd|Empowerment|Empowerment Patient|Self Efficacy
Zahide Aksoy|The Scientific and Technological Research Council of Turkey|Marmara University
 February 15 2024 Not Applicable
NCT05743179 Recruiting
Hip Fractures|Pneumonia
The University of Hong Kong|Queen Mary Hospital Hong Kong|Caritas Medical Centre Hong Kong|Prince of Wales Hospital Shatin Hong Kong|United Christian Hospital
 December 5 2022 Phase 4
NCT02864784 Withdrawn
Castrate Resistant Prostate Cancer With Bone Metastasis
Amorphical Ltd.
 June 2022 Phase 1
NCT04957641 Completed
Hereditary Angioedema
Takeda
 April 21 2022 --
NCT05213286 Unknown status
Autism Spectrum Disorder|Schizotypal Disorder
Glostrup University Hospital Copenhagen
 February 1 2022 Not Applicable

Domande Frequenti (Frequently Asked Questions)

Domanda 1:
How can I reconstitute it for in vivo studies?

Risposta:
Please dissolve it directly to 30% PEG400+0.5% Tween80+5% Propylene glycol.