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CCT137690 Aurora Kinase inhibitor

Cat.No.S2744

CCT137690 is a highly selective inhibitor of Aurora A, Aurora B and Aurora C with IC50 of 15 nM, 25 nM and 19 nM. It has little effect on hERG ion-channel.
CCT137690 Aurora Kinase inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 551.48

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Quality Control

Batch: Purity: 99.92%
99.92

Solubility

In vitro
Batch:

DMSO : 12 mg/mL (21.75 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Ethanol : Insoluble

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In vivo
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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.

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Chemical Information, Storage & Stability

Molecular Weight 551.48 Formula

C26H31BrN8O

 Storage (From the date of receipt)
CAS No. 1095382-05-0 Download SDF Storage of Stock Solutions

Synonyms N/A Smiles CC1=CC(=NO1)CN2CCN(CC2)C3=C4C(=NC=C3Br)N=C(N4)C5=CC=C(C=C5)N6CCN(CC6)C

Mechanism of Action

Targets/IC50/Ki
Aurora A
15 nM
Aurora C
19 nM
Aurora B
25 nM
In vitro
CCT137690 displays antiproliferative activity in a range of human tumor cell lines, including SW620 colon carcinoma cell and A2780 ovarian cancer cell with GI50 of 0.3 and o.14 μM, respectively. In addition, this compound also inhibit the phosphorylation of histone H3. It inhibits the major cytochrome P450 isoforms (CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP3A4) with IC50 greater than 10 μM. However, it is a moderate inhibitor of the hERG ion-channel with IC50 of 3.0 μM. This chemical effectively inhibits the growth of human tumor cell lines of different origins with GI50 ranging from 0.005 to 0.47 μM. It completely inhibits both Aurora A autophosphorylation at T288 and histone H3 phosphorylation at 0.5 μM. It induces polyploidy, mitotic aberrations, and apoptosis in HCT116 cells. It reduces MYCN levels and GSK3β phosphorylation in the KELLY neuroblastoma cell line. It inhibits autophosphorylation of FLT3 and phosphorylation of its downstream targets STAT5 and p44/42 MAPK (Erk1/2).
Kinase Assay
Flashplate assay for identification and evaluation of Aurora inhibitors
On this assay 384-well Basic Flashplate® as solid assay platform is used. The plates are coated overnight at 4 °C with dithiothreitol (DTT) at 100 μg/mL in PBS buffer and used after being washed twice with PBS. 5 μL of CCT137690 in 2% DMSO is added to each well followed by 15 μL master mix of kinase buffer (50 mM Tris pH 7.5, 10 mM NaCl, 2.5 mM MgCl2, 1 mM myelin basic protein (MBP), 20 μM ATP, and 0.025 μCi/μL 33P-ATP). Finally, 250 ng per well of Aurora-A enzyme is added. The plate is shaken for approximately 2 min on a flat-bed plate shaker and incubated for 2 hours at room temperature. The reaction is stopped by washing the plate twice on a 16-pin wash with 10 mM sodium pyrophosphate. The plate is then read on a TopCount-NXTTM. For the determination of the inhibitory activity against Aurora-B or Aurora-C, the same conditions are followed in the assay using Aurora-B or Aurora-C enzymes.
In vivo
CCT137690 is highly orally bioavailable and inhibits the growth of SW620 colon carcinoma xenografts with no observed toxicities as defined by body weight loss. This compound inhibits growth of MYCN-induced neuroblastoma at a dose of 100 mg/kg. Additionally, it achieves target modulation and potently inhibits the growth of subcutaneous MOLM-13 xenografts, with no obvious toxicity or loss of body weight.
References

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