Home Cell Cycle Aurora Kinase inhibitor - VEGFR inhibitor CYC116 For research use only.

CYC116

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.

CYC116 Chemical Structure

CYC116 Chemical Structure

CAS No. 693228-63-6

Purity & Quality Control

CYC116 Related Products

Signaling Pathway

Aurora Kinase Signaling Pathways

Aurora Kinase Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
A2780 cells Cytotoxicity assay 96 h Cytotoxicity against human A2780 cells after 96 hrs by MTT assay 20462263
MIAPaCa2 cells Cytotoxicity assay 96 h Cytotoxicity against human MIAPaCa2 cells after 96 hrs by MTT assay 20462263
HT-29 cells Cytotoxicity assay 96 h Cytotoxicity against human HT-29 cells after 96 hrs by MTT assay 20462263
MCF7 cells Cytotoxicity assay 96 h Cytotoxicity against human MCF7 cells after 96 hrs by MTT assay 20462263
HeLa cells Cytotoxicity assay 96 h Cytotoxicity against human HeLa cells after 96 hrs by MTT assay 20462263
COLO205 cells Cytotoxicity assay 96 h Cytotoxicity against human COLO205 cells after 96 hrs by MTT assay 20462263
HCT116 cells Cytotoxicity assay 96 h Cytotoxicity against human HCT116 cells after 96 hrs by MTT assay 20462263
K562 cells Cytotoxicity assay 96 h Cytotoxicity against human K562 cells after 96 hrs by MTT assay 20462263
CCRF-CEM cells Cytotoxicity assay 96 h Cytotoxicity against human CCRF-CEM cells after 96 hrs by MTT assay 20462263
MV4-11 cells Cytotoxicity assay 96 h Cytotoxicity against human MV4-11 cells after 96 hrs by MTT assay 20462263
HL60 cells Cytotoxicity assay 96 h Cytotoxicity against human HL60 cells after 96 hrs by MTT assay 20462263
NCI-H460 cells Cytotoxicity assay 96 h Cytotoxicity against human NCI-H460 cells after 96 hrs by MTT assay 20462263
MESSA cells Cytotoxicity assay 96 h Cytotoxicity against human MESSA cells after 96 hrs by MTT assay 20462263
U2OS cells Function assay 0.07-10 uM 2 h Inhibition of Aurora kinase in nocodazole-synchronized human U2OS cells assessed as reduction of histone H3 serine-10 phosphorylation at 0.07 to 10 uM after 2 hrs immunofluorescence microscopy 20462263
A549 cells Function assay 0.5-2 μM 7 h Cell cycle arrest in asynchronous human A549 cells assessed as accumulation of cyclin B1-negative tetraploid cells at G1 phase at 0.5 to 2 uM after 7 hrs by FACS analysis 20462263
SW620 cells Function assay 1 μM 48 h Effect on mitotic index in human SW620 cells assessed as appearance of polyploid cells at 1 uM after 48 hrs by propidium iodide staining-based FACS analysis 20462263
HeLa cells Function assay 1.25 μM 7 h Inhibition of Aurora kinase in human HeLa cells assessed as complete inhibition of histone H3 phosphorylation at 1.25 uM after 7 hrs by Western blot analysis 20462263
A549 cells Function assay 7 h Inhibition of Aurora kinase in human A549 cells assessed as concentration required for half-maximal inhibition of histone H3 serine-10 phosphorylation after 7 hrs immunofluorescence microscopy 20462263
BxPC3 cells Cytotoxicity assay 96 h Cytotoxicity against human BxPC3 cells after 96 hrs by MTT assay 20462263
HUPT4 cells Cytotoxicity assay 96 h Cytotoxicity against human HUPT4 cells after 96 hrs by MTT assay 20462263
Saos2 cells Cytotoxicity assay 96 h Cytotoxicity against human Saos2 cells after 96 hrs by MTT assay 20462263
Click to View More Cell Line Experimental Data

Biological Activity

Description 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.
Features An orally bioavailable, small molecule inhibitor of Aurora kinase/VEGFR2.
Targets
Aurora A [1]
(Cell-free assay)		 Aurora B [1]
(Cell-free assay)		 VEGFR2 [1]
(Cell-free assay)		 FLT3 [1]
(Cell-free assay)		 CDK2/CyclinE [1]
(Cell-free assay)		 Click to View More Targets
8 nM(Ki) 9 nM(Ki) 44 nM(Ki) 44 nM(Ki) 0.39 μM(Ki)
In vitro
In vitro The most Aurora-selective CYC116 shows inhibitory effect on Aurora A and B kinases 50-fold more potently than any of the CDKs assayed. [1] 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. [1] 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. [1]
Kinase Assay 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.
Cell Research Cell lines HeLa, MCF7, MV4-11 and A2780 cells
Concentrations 0-10 μM
Incubation Time 72 or 96 hours
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.
In Vivo
In vivo 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. [1]
Animal Research Animal Models NCI-H460 cells are implanted intraperitoneally into the mice.
Dosages 75 and 100 mg/kg
Administration Administered via p.o.

Chemical Information & Solubility

Molecular Weight 368.46 Formula

C18H20N6OS
CAS No. 693228-63-6 SDF Download CYC116 SDF
Smiles CC1=C(SC(=N1)N)C2=NC(=NC=C2)NC3=CC=C(C=C3)N4CCOCC4
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 24 mg/mL ( (65.13 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


Molecular Weight Calculator

In vivo
Batch:

Add solvents to the product individually and in order.


In vivo Formulation Calculator

Preparing Stock Solutions

Molarity Calculator

Mass Concentration Volume Molecular Weight

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3
If you have any other enquiries, please leave a message.

* Indicates a Required Field

Please enter your name.
Please enter your email. Please enter a valid email address.
Please write something to us.
Tags: buy CYC116 | CYC116 supplier | purchase CYC116 | CYC116 cost | CYC116 manufacturer | order CYC116 | CYC116 distributor