Home Apoptosis Apoptosis related Inductor Zoledronic acid (Zoledronate)

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Zoledronic acid (Zoledronate) Botresorptieremmer

Cat.nr.: S1314

Zoledronic acid (Zoledronate), een krachtige osteoclastenremmer, induceert apoptose in osteoclasten door enzymen van de mevalonaatroute te remmen en de isoprenylering van kleine GTP-bindende eiwitten zoals Ras en Rho te voorkomen. Zoledronic acid (ZA) induceert ook autofagie.
Zoledronic acid (Zoledronate) Apoptosis related Inductor Chemical Structure

Chemische structuur

Molecuulgewicht: 272.09

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Kwaliteitscontrole (Quality Control)

Batch: Zuiverheid: 99.80%
99.80

Celkweek, behandeling & werkzame concentratie
(Cell Culture, Treatment & Working Concentration)

Cellijnen Assaytype Concentratie Incubatietijd Formulering Activiteitsbeschrijving 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
Klik om meer experimentele gegevens over cellijnen te bekijken

Chemische informatie, opslag en stabiliteit (Chemical Information, Storage & Stability)

Molecuulgewicht 272.09 Formule

C5H10N2O7P2

 Opslag (vanaf de datum van ontvangst)
CAS-nr. 118072-93-8 SDF downloaden Opslag van stamoplossingen

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

Oplosbaarheid (Solubility)

In vitro
Batch:

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
(Met vocht verontreinigd DMSO kan de oplosbaarheid verminderen. Gebruik verse, watervrije DMSO.)

Molariteitscalculator

Massa Concentratie Volume Molecuulgewicht
Verdunningscalculator Molecuulgewichtcalculator

In vivo
Batch:

In vivo formulatiecalculator (heldere oplossing)

Stap 1: Voer onderstaande informatie in (Aanbevolen: een extra dier om rekening te houden met verlies tijdens het experiment)

mg/kg g μL

Stap 2: Voer de in vivo formulering in (Dit is alleen de calculator, geen formulering. Neem eerst contact met ons op als er geen in vivo formulering is in de sectie oplosbaarheid.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Berekeningsresultaten:

Werkconcentratie: mg/ml;

Methode voor het bereiden van DMSO-moedervloeistof: mg geneesmiddel vooropgelost in μL DMSO ( Concentratie moedervloeistof mg/mL, Neem eerst contact met ons op als de concentratie de DMSO-oplosbaarheid van de batch van het geneesmiddel overschrijdt. )

Methode voor het bereiden van in vivo formulering: Neem μL DMSO moedervloeistof, voeg daarna toeμL PEG300, mengen en verhelderen, daarna toevoegenμL Tween 80, mengen en verhelderen, daarna toevoegen μL ddH2O, mengen en verhelderen.

Methode voor het bereiden van in vivo formulering: Neem μL DMSO moedervloeistof, voeg daarna toe μL Maïsolie, mengen en verhelderen.

Opmerking: 1. Zorg ervoor dat de vloeistof helder is voordat u het volgende oplosmiddel toevoegt.
2. Zorg ervoor dat u het/de oplosmiddel(en) in de juiste volgorde toevoegt. U moet ervoor zorgen dat de verkregen oplossing, bij de vorige toevoeging, een heldere oplossing is voordat u verdergaat met het toevoegen van het volgende oplosmiddel. Fysieke methoden zoals vortexen, ultrasoon of een warmwaterbad kunnen worden gebruikt om het oplossen te bevorderen.

Werkingsmechanisme (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.

Referenties

Toepassingen (Applications)

Methoden Biomarkers Afbeeldingen PMID
Western blot ALDH1 / Oct4 / Nanog / Sox2 / CD49f N-cadherin / E-cadherin / Vimentin
S1314-WB1
30791957
Growth inhibition assay Cell viability
S1314-viability1
30791957

Informatie over klinische proeven (Clinical Trial Information)

(gegevens van https://clinicaltrials.gov, bijgewerkt op 2024-05-22)

NCT-nummer Werving Aandoeningen Sponsor/medewerkers Startdatum Fasen
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

Veelgestelde vragen (Frequently Asked Questions)

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

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