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Home > Products > Epigenetics > Aurora Kinase Inhibitor > CYC116 693228-63-6

CYC116 693228-63-6

Product Description

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Molecular Weight:

368.46 CYC116 is a Potent Inhibitor of Aurora A/B with Ki of 8.0 nM/9.2 nM, is less potent to VEGFR2 (Ki of 44 nM), with 50-fold greater potency than CDKs, not active against PKA, Akt/PKB, PKC, no effect on GSK-3α/β, CK2, Plk1 and SAPK2A. Phase 1.


Biological Activity


The most Aurora-selective CYC116 shows inhibitory effect on Aurora A
and B kinases 50-fold more potently than any of the CDKs assayed. CYC116 is initially screened against a panel of human leukemia and
solid tumor cell lines using an MTT antiproliferative assay. The results
show that CYC116 has broad-spectrum antitumor activity and shows
specific cytotoxicity against the acute myelogenous leukemia cell line
MV4-11 with IC50 of 34 nM.


In addition,
anti-proliferative activity of CYC116 is found to be associated with
Aurora A and B modulation such as, inhibition of Aurora
autophosphorylation, reduction of histone H3 phosphorylation,
polyploidy, followed by cell death, resulting from a failure in
cytokinesis.


Mice bearing subcutaneous NCI-H460 xenografts are given CYC116 orally
for 5 days, at dose levels of 75 and 100 mg/kg q.d. It leads to tumor
growth delays of 2.3 and 5.8 days, which translated into specific growth
delays of 0.32 and 0.81, respectively.






Kinase Assays


Aurora A kinase assays are performed using a 25 μL reaction volume (25
mM β-glycerophosphate, 20 mM Tris/HCl, pH 7.5, 5 mM EGTA, 1 mM DTT, 1 mM
Na3VO4, 10 μg of kemptide (peptide substrate)).
Recombinant Aurora A kinase is diluted in 20 mM Tris/HCl, pH 8,
containing 0.5 mg/mL BSA, 2.5% glycerol, and 0.006% Brij-35.


Reactions
are started by the addition of 5 μL Mg/ATP mix (15 mM MgCl2, 100 μM ATP, with 18.5 kBq γ-32P-ATP per well) and incubated at 30°C for 30 minutes before termination with 25 μL of 75 mM H3PO4.
Aurora B kinase assays are performed like Aurora A except that prior to
use, Aurora B is activated in a separate reaction at 30°C for 60
minutes with inner centromere protein.


Method






Standard MTT assays are performed. In short, cells are seeded into
96-well plates according to doubling time and incubated overnight at
37°C. Test compounds are made up in DMSO, a 3-fold dilution series is
prepared in 100 μL of cell medium, added to cells (in triplicates) and
incubated for 72 or 96 hours at 37°C. MTT is made up as a stock of 5
mg/mL in cell medium, and the solution is filter-sterilized.


Medium is
removed from the cells followed by a wash with PBS. MTT solution is then
added at 20 μL/well and incubated in the dark at 37°C for 4 hours. MTT
solution is removed and cells are again washed with 200 μL of PBS. MTT
dye is solubilized with 200 μL/well of DMSO by agitation. Absorbance is
read at 540 nm and data analyzed using curve-fitting software to
determine IC50 values.




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Product Categories : Epigenetics > Aurora Kinase Inhibitor