Fig. 1 · Structure

Documents & Downloads

ZM-447439

Cat. No. A11009 CAS 331771-20-1

Aurora Kinase inhibitor

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.

In Stock

Free Aliquoting for Your Order

Tell us your preferred amount per vial. We’ll confirm the options.

Biological Activity

Target & Activity

Target Activity Value
AuroraA IC50 110nM
AuroraB IC50 130nM
LCK IC50 880nM
Src IC50 1.03μM
MEK1 IC50 1.79μM
CDK1 IC50 >10μM
CDK2 IC50 >10μM
CDK4 IC50 >10μM
PLK1 IC50 >10μM
Chk1 IC50 >10μM
IKK1 IC50 >10μM
IKK2 IC50 >10μM
cFLT2 IC50 >10μM
KDR2 IC50 >10μM
ZAP70 IC50 >10μM
FAK IC50 >10μM

16 targets · Scroll to view more

Cellular Effect

Cell Line Activity Value Description Reference
A549 IC50 3.3 μM Antiproliferative activity against human A549 cells after 72 hrs by MTT-based WST8 reagent assay [PMID: 25270403]
HepG2 IC50 1.4 μM Antiproliferative activity against human HepG2 cells after 72 hrs by sulforhodamine B assay [PMID: 28279846]
HT-29 IC50 2.2 μM Antiproliferative activity against human HT-29 cells after 72 hrs by MTT-based WST8 reagent assay [PMID: 25270403]
K562 IC50 > 100 μM Antiproliferative activity against human K562 cells after 72 hrs by MTT-based WST8 reagent assay [PMID: 25270403]
LoVo IC50 1.9 μM Antiproliferative activity against human LoVo cells after 72 hrs by MTT-based WST8 reagent assay [PMID: 25270403]
NCI-H661 IC50 2.9 μM Antiproliferative activity against human NCI-H661 cells after 72 hrs by MTT-based WST8 reagent assay [PMID: 25270403]
U-937 IC50 > 100 μM Antiproliferative activity against human U937 cells after 72 hrs by MTT-based WST8 reagent assay [PMID: 25270403]

In Vitro Studies

In proliferating MCF-7 cells exposed to ZM-447439 for 72 h, cloning efficiency was reduced to below 40% at 1.25 μM and 2.5 μM. In HeLa cells treated with MPS1-IN-1 followed by ZM-447439, the slope of kinetochore Dsn1S109ph versus distance from the midzone differed significantly between control and ZM-447439-treated cells (p < 0.0001, F test). In HT1080 cells carrying an autonomously propagated EGFP-HAC, treatment at 1 μM for 3 days yielded 70.4 ± 0.5% cells with EGFP. Following a 12-h nocodazole block, 4% of mitotic HeLa cells treated with 2 μM ZM-447439 remained in mitosis after 1 h, compared with 67% of controls. [1,2,3]

Literature-reported observations and conditions; not Adooq-tested protocols or general treatment recommendations.

Reduced Cloning Efficiency in Proliferating MCF-7 Cells

Cell-based study · proliferating MCF-7 cells [1]

Proliferating MCF-7 cells were exposed to ZM-447439 for 72 h. At 1.25 μM and 2.5 μM, cloning efficiency was reduced to below 40%.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
cloning efficiencycloning efficiency below 40%[1]

Literature-Reported Treatment Conditions

Treatment concentration
1.25 μM and 2.5 μM
Exposure duration
exposed to ZM447439 for 72 h
Method
ZM447439 was then added
Vehicle
DMSO
Methods and source locations

Compound reported in the paper: ZM-447439

Literature evidence for the named compound in the stated model; no Adooq product-use or lot-performance claim.

Results > ZM447439-induced endoreduplication is enhanced in the absence of p53 function (S21); Materials and methods > Cell culture (S141); Materials and methods > Cell cycle analysis and cloning assays (S147, S149, S150); Figure 2. legend (S179)

cloning efficiency: cloning efficiency; comparator: DMSO-treated controls — Results > ZM447439-induced endoreduplication is enhanced in the absence of p53 function (S21); Materials and methods > Cell cycle analysis and cloning assays (S150)

Kinetochore Phosphorylation Gradient in HeLa Cells

Cell-based study · HeLa cells [2]

HeLa cells were treated with MPS1-IN-1 and then with 10 μM ZM447439 for 15 min, prior to fixation. For ZM447439-treated cells, slope = 0.12 and is not significantly different from zero (p = 0.48). The slopes are significantly different from one another (p < 0.0001, F test).

Measured endpoints — not treatment concentrations
EndpointReported resultReference
Dsn1S109ph at individual kinetochores as a function of distance from the midzoneReported result HeLa cells were treated with MPS1-IN-1 and then with 10 μM ZM447439 for 15 min, prior to fixation. For ZM447439-treated cells, slope = 0.12 and is not significantly different from zero (p = 0.48). The slopes are significantly different from one another (p < 0.0001, F test).[2]

Literature-Reported Treatment Conditions

Treatment concentration
10 μM
Exposure duration
for 15 min, prior to fixation
Co-treatment
Other interventions in this design: MPS1-IN-1 10 μM. Compound effect isolated by the comparison: nine control and five ZM447439-treated cells.
Reported limits
Not stated in the sentences used: route, vehicle. Removed after verification: value.
Methods and source locations

Compound reported in the paper: ZM-447439

Literature evidence for the named compound in the stated model; no Adooq product-use or lot-performance claim.

Results > Anaphase phosphorylation of Dsn1 requires the central spindle-dependent gradient of Aurora B activity (S25, S28, S29); STAR★Methods > Method details > Cell treatments (S156); Figure 2 legend (S200, S203)

Dsn1S109ph at individual kinetochores as a function of distance from the midzone: Dsn1S109ph at individual kinetochores as a function of distance from the midzone; comparator: nine control — Results > Anaphase phosphorylation of Dsn1 requires the central spindle-dependent gradient of Aurora B activity (S25, S28, S29); Figure 2 legend (S200, S203)

EGFP Readout in Cells Carrying an Autonomously Propagated HAC

Cell-based study · HT1080 cells with an autonomously propagated EGFP-HAC [3]

HT1080 cells with an autonomously propagated EGFP-HAC were treated at 1 μM for 3 days. The proportion of cells with EGFP was 70.4 ± 0.5%.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
% Cells with EGFPCells with EGFP 70.4 ± 0.5%[3]

Literature-Reported Treatment Conditions

Treatment concentration
1 μM
Exposure duration
3 days
Reported limits
Not stated in the sentences used: route, vehicle.
Methods and source locations

Compound reported in the paper: ZM-447439

Literature evidence for the named compound in the stated model; no Adooq product-use or lot-performance claim.

Results > Effect of aneugens and clastogens on the rate of HAC mis-segregation during mitotic divisions (S120); Table 1 (T1.h1, T1.r12); Table 3 (T3.h2, T3.r1, T3.r10)

% Cells with EGFP: % Cells with EGFP; comparator: No drug — Table 1 (T1.r12); Table 3 (T3.h2, T3.r10)

Mitotic Index in HeLa Cells Following Nocodazole Block

Cell-based study · Mitotic HeLa cells [1]

Mitotic HeLa cells received 2 μM ZM-447439 following a 12-h nocodazole block. After 1 h, only 4% of ZM-447439-treated cells remained in mitosis, compared with 67% of controls.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
mitotic index, as determined by MPM-2 reactivitymitotic index 4%[1]

Literature-Reported Treatment Conditions

Treatment concentration
2 μM
Exposure duration
after a 12-h nocodazole block; after 1 h
Method
replated in various drug combinations
Vehicle
DMSO
Co-treatment
Other interventions in this design: nocodazole. Compound effect isolated by the comparison: only 4% of the ZM447439-treated cells were still in mitosis, compared with 67% of the controls.
Methods and source locations

Compound reported in the paper: ZM-447439

Literature evidence for the named compound in the stated model; no Adooq product-use or lot-performance claim.

Results > ZM447439 compromises spindle checkpoint function (S56, S63); Materials and methods > Cell culture (S141, S143, S144); Figure 5. legend (S199, S201)

mitotic index, as determined by MPM-2 reactivity: mitotic index, as determined by MPM-2 reactivity; comparator: controls — Results > ZM447439 compromises spindle checkpoint function (S63); Materials and methods > Cell culture (S143); Figure 5. legend (S199, S201)

Specifications

Manufacturer Adooq Bioscience
Actions Inhibitor
CAS Number 331771-20-1
Applications Aurora Kinase inhibitor
Formula C29H31N5O4
Molecular Weight 513.6
SMILES
COC1=C(C=C2C(=C1)C(=NC=N2)NC3=CC=C(C=C3)NC(=O)C4=CC=CC=C4)OCCCN5CCOCC5

Storage & Solubility

In Vitro Solubility

Reported Solubility

SolventReported Solubility
DMSO 90 mg/mL (175.23 mM)
Water Insoluble
Ethanol Insoluble

Preparing Stock Solutions

Stock preparation is unavailable for this product molecular weight.

Calculated stock concentrations do not establish solvent solubility. Refer to the reported solubility data for experimental guidance.

In Vivo Preparation

Concentration
28 mg/mL
Vehicle
30% PEG400+0.5% Tween80+5% propylene glycol

Storage

Store powder at -20°C, keep desiccated.
In powder form, the chemical is stable for 36 months.
In solution, store at -20°C and use within 1 month to prevent loss of potency. Aliquot to avoid multiple freeze/thaw cycles.

Research References

  1. [1] Ditchfield C, Johnson VL, Tighe A, et al. Aurora B couples chromosome alignment with anaphase by targeting BubR1, Mad2, and Cenp-E to kinetochores. J Cell Biol (2003). PMID: 12719470 DOI: 10.1083/jcb.200208091 Source material
  2. [2] Papini D, Levasseur MD, Higgins JMG. The Aurora B gradient sustains kinetochore stability in anaphase. Cell Rep (2021). PMID: 34758321 DOI: 10.1016/j.celrep.2021.109818 Source material
  3. [3] Lee HS, Lee NC, Grimes BR, et al. A new assay for measuring chromosome instability (CIN) and identification of drugs that elevate CIN in cancer cells. BMC Cancer (2013). PMID: 23694679 DOI: 10.1186/1471-2407-13-252 Source material

Added to your cart

View Cart Checkout
Loading...