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ZM 447439 Aurora A/B Inhibitor

Cat.nr.: S1103

ZM 447439 is a selective and ATP-competitive inhibitor for Aurora A and Aurora B with IC50 of 110 nM and 130 nM, respectively. It is more than 8-fold selective for Aurora A/B than MEK1, Src, Lck and has little effect against CDK1/2/4, Plk1, Chk1, etc.
ZM 447439 Aurora Kinase inhibitor Chemical Structure

Chemische structuur

Molecuulgewicht: 513.59

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Kwaliteitscontrole (Quality Control)

Batch: Zuiverheid: 99.26%
99.26

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

Cellijnen Assaytype Concentratie Incubatietijd Formulering Activiteitsbeschrijving PMID
human EoL-1-cell Growth inhibition assay Inhibition of human EoL-1-cell cell growth in a cell viability assay, IC50=0.18678 μM
MCF7 cell Proliferation assay Antiproliferative activity against MCF7 cell line, IC50=0.198 μM
human P12-ICHIKAWA cell Growth inhibition assay Inhibition of human P12-ICHIKAWA cell growth in a cell viability assay, IC50=0.22441 μM
human KARPAS-45 cell Growth inhibition assay Inhibition of human KARPAS-45 cell growth in a cell viability assay, IC50=0.38128 μM
human ES3 cell Growth inhibition assay Inhibition of human ES3 cell growth in a cell viability assay, IC50=0.4732 μM
human ES8 cell Growth inhibition assay Inhibition of human ES8 cell growth in a cell viability assay, IC50=0.49806 μM
human TE-11 cell Growth inhibition assay Inhibition of human TE-11 cell growth in a cell viability assay, IC50=0.53703 μM
human RS4-11 cell Growth inhibition assay Inhibition of human RS4-11 cell growth in a cell viability assay, IC50=0.5544 μM
human MOLT-16 cell Growth inhibition assay Inhibition of human MOLT-16 cell growth in a cell viability assay, IC50=0.60961 μM
human RKO cell Growth inhibition assay Inhibition of human RKO cell growth in a cell viability assay, IC50=0.70656 μM
human MV-4-11 cell Growth inhibition assay Inhibition of human MV-4-11 cell growth in a cell viability assay, IC50=0.7963 μM
human SW954 cell Growth inhibition assay Inhibition of human SW954 cell growth in a cell viability assay, IC50=0.83635 μM
human BE-13 cell Growth inhibition assay Inhibition of human BE-13 cell growth in a cell viability assay, IC50=0.84418 μM
human MOLT-4 cell Growth inhibition assay Inhibition of human MOLT-4 cell growth in a cell viability assay, IC50=0.89978 μM
human NBsusSR cell Growth inhibition assay Inhibition of human NBsusSR cell growth in a cell viability assay, IC50=0.91387 μM
human H9 cell Growth inhibition assay Inhibition of human H9 cell growth in a cell viability assay, IC50=0.92979 μM
human A172 cell Growth inhibition assay Inhibition of human A172 cell growth in a cell viability assay, IC50=0.98411 μM
human ES5 cell Growth inhibition assay Inhibition of human ES5 cell growth in a cell viability assay, IC50=1.00248 μM
human SBC-1 cell Growth inhibition assay Inhibition of human SBC-1 cell growth in a cell viability assay, IC50=1.03928 μM
human NCI-H209 cell Growth inhibition assay Inhibition of human NCI-H209 cell growth in a cell viability assay, IC50=1.16602 μM
human NKM-1 cell Growth inhibition assay Inhibition of human NKM-1 cell growth in a cell viability assay, IC50=1.16798 μM
human NCI-H720 cell Growth inhibition assay Inhibition of human NCI-H720 cell growth in a cell viability assay, IC50=1.20627 μM
human KE-37 cell Growth inhibition assay Inhibition of human KE-37 cell growth in a cell viability assay, IC50=1.21388 μM
human SW48 cell Growth inhibition assay Inhibition of human SW48 cell growth in a cell viability assay, IC50=1.23155 μM
human IST-SL1 cell Growth inhibition assay Inhibition of human IST-SL1 cell growth in a cell viability assay, IC50=1.31727 μM
human SK-NEP-1 cell Growth inhibition assay Inhibition of human SK-NEP-1 cell growth in a cell viability assay, IC50=1.36498 μM
human NOMO-1 cell Growth inhibition assay Inhibition of human NOMO-1 cell growth in a cell viability assay, IC50=1.36725 μM
human DOHH-2 cell Growth inhibition assay Inhibition of human DOHH-2 cell growth in a cell viability assay, IC50=1.40276 μM
human ABC-1 cell Growth inhibition assay Inhibition of human ABC-1 cell growth in a cell viability assay, IC50=1.40352 μM
human Ramos-2G6-4C10 cell Growth inhibition assay Inhibition of human Ramos-2G6-4C10 cell growth in a cell viability assay, IC50=1.40605 μM
human EM-2 cell Growth inhibition assay Inhibition of human EM-2 cell growth in a cell viability assay, IC50=1.41721 μM
human NB14 cell Growth inhibition assay Inhibition of human NB14 cell growth in a cell viability assay, IC50=1.55621 μM
human MOLT-13 cell Growth inhibition assay Inhibition of human MOLT-13 cell growth in a cell viability assay, IC50=1.56706 μM
human ECC10 cell Growth inhibition assay Inhibition of human ECC10 cell growth in a cell viability assay, IC50=1.63353 μM
human LK-2 cell Growth inhibition assay Inhibition of human LK-2 cell growth in a cell viability assay, IC50=1.64594 μM
human CTB-1 cell Growth inhibition assay Inhibition of human CTB-1 cell growth in a cell viability assay, IC50=1.67082 μM
human NCI-H1581 cell Growth inhibition assay Inhibition of human NCI-H1581 cell growth in a cell viability assay, IC50=1.6755 μM
human COLO-800 cell Growth inhibition assay Inhibition of human COLO-800 cell growth in a cell viability assay, IC50=1.70382 μM
human NB7 cell Growth inhibition assay Inhibition of human NB7 cell growth in a cell viability assay, IC50=1.75297 μM
human LAMA-84 cell Growth inhibition assay Inhibition of human LAMA-84 cell growth in a cell viability assay, IC50=1.7552 μM
human HCT-116 cells Growth inhibition assay Inhibition of human HCT-116 cell growth in a cell viability assay, IC50=1.80908 μM
SK-UT-1 cell Growth inhibition assay Inhibition of human SK-UT-1 cell growth in a cell viability assay, IC50=1.8153 μM
human H4 cell Growth inhibition assay Inhibition of human H4 cell growth in a cell viability assay, IC50=1.81578 μM
human CAL-51 cell Growth inhibition assay Inhibition of human CAL-51 cell growth in a cell viability assay, IC50=1.83845 μM
human LoVo cells Proliferation assay 72 h Antiproliferative activity against human LoVo cells after 72 hrs by MTT-based WST8 reagent assay, IC50=1.9 μM
human HN cell Growth inhibition assay Inhibition of human HN cell growth in a cell viability assay, IC50=1.9251 μM
human L-363 cell Growth inhibition assay Inhibition of human L-363 cell growth in a cell viability assay, IC50=1.9512 μM
human NCI-H747 cell Growth inhibition assay Inhibition of human NCI-H747 cell growth in a cell viability assay, IC50=2.03353 μM
human A498 cell Growth inhibition assay Inhibition of human A498 cell growth in a cell viability assay, IC50=2.3669 μM
Klik om meer experimentele gegevens over cellijnen te bekijken

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

Molecuulgewicht 513.59 Formule

C29H31N5O4

 Opslag (vanaf de datum van ontvangst)
CAS-nr. 331771-20-1 SDF downloaden Opslag van stamoplossingen

Synoniemen N/A Smiles COC1=C(C=C2C(=C1)C(=NC=N2)NC3=CC=C(C=C3)NC(=O)C4=CC=CC=C4)OCCCN5CCOCC5

Oplosbaarheid (Solubility)

In vitro
Batch:

DMSO : 103 mg/mL (200.54 mM)
(Met vocht verontreinigd DMSO kan de oplosbaarheid verminderen. Gebruik verse, watervrije DMSO.)

Water : Insoluble

Ethanol : Insoluble

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)

Kenmerken
An Aurora selective ATP-competitive inhibitor.
Targets/IC50/Ki
Aurora A
(Cell-free assay)
110 nM
Aurora B
(Cell-free assay)
130 nM
LCK
(Cell-free assay)
880 nM
Src
(Cell-free assay)
1.03 μM
MEK1
(Cell-free assay)
1.79 μM
In vitro

In vitro, ZM-447439 selectively inhibits recombinant human Aurora A and B with IC50 values of 110 and 130 nM, respectively, while other protein kinases of diverse structural types including the mitotic kinases CDK1 and PLK1 are inhibited with IC50 values >10 μM. Aurora kinase inhibitor, ZM-447439 time- and dose-dependently inhibits the growth of all three cell lines with IC50 values of 3 μM (BON), 0.9 μM (QGP-1) and 3 μM (MIP-101) after 72 hours of continuous exposure. In addition, ZM-447439 potently induces cell apoptosis by promoting DNA fragmentation and caspase 3 and 7 activation, and arrests GEP-NET cells in the G0 /G1and G2/M phase of the cell cycle. In mouse embryo, inhibition of Aurora kinase activity by ZM-447439 results in abnormalities during mitosis by regulating the phosphorylation of histone H3 serine 10 (H3S10Ph) from G2 to metaphase with different perturbations in each embryonic cycle. A recent study shows that ZM-447439 exhibits growth inhibitory and proapoptotic effect on cervical cancer SiHa cells, and enhances the chemosensitivity.

Kinase Assay
In vitro kinase-assays
Recombinant Aurora A en B worden uitgedrukt als NH2-terminale His6-getagde fusie-eiwitten met behulp van een baculovirus-expressiesysteem. Aurora A wordt gezuiverd door affiniteitschromatografie met Ni-NTA-agarose, en Aurora B wordt gezuiverd door ionenuitwisselingschromatografie met CM Sepharose Fast Flow. 1 ng gezuiverd recombinant enzym wordt toegevoegd aan een reactiecocktail die 25 mM Tris-HCl, pH 7,5, 12,5 mM KCl, 2,5 mM NaF, 0,6 mM DTT, 6,25 mM MnCl2, 10 μM peptidesubstraat, 10 μM voor Aurora A of 5 μM ATP voor Aurora B, en 0,2 μCi γ-[33P]ATP (specifieke activiteit ≥2.500 Ci/mmol) bevat, en wordt vervolgens 60 minuten bij kamertemperatuur geïncubeerd. Reacties worden gestopt door toevoeging van 20% fosforzuur, en de producten worden opgevangen op P30-nitrocellulosefilters en getest op incorporatie van 33P met een BetaplateTM-teller. Geen enzym- en geen samengestelde controlewaarden worden gebruikt om de concentratie van ZM447439 te bepalen, die 50% remming van de enzymactiviteit gaf. Verdere details zijn op aanvraag verkrijgbaar bij Nicholas Keen.
Referenties
  • [4] https://pubmed.ncbi.nlm.nih.gov/21159048/

Toepassingen (Applications)

Methoden Biomarkers Afbeeldingen PMID
Western blot p53 / p21 / p-p38 / p38 pHistone H3 / CEM BubR1 / MAD2 / Cyclin B1
S1103-WB1
23759594
Immunofluorescence p21 p53 Aurora B / Survivin
S1103-IF1
23759594