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1095382-05-0 molecular structure
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1-{6-bromo-2-[4-(4-methylpiperazin-1-yl)phenyl]-3H-imidazo[4,5-b]pyridin-7-yl}-4-[(5-methyl-1,2-oxazol-3-yl)methyl]piperazine

ChemBase ID: 73305
Molecular Formular: C26H31BrN8O
Molecular Mass: 551.48134
Monoisotopic Mass: 550.18041965
SMILES and InChIs

SMILES:
c1(cnc2c(c1N1CCN(CC1)Cc1cc(on1)C)nc([nH]2)c1ccc(cc1)N1CCN(CC1)C)Br
Canonical SMILES:
CN1CCN(CC1)c1ccc(cc1)c1nc2c([nH]1)ncc(c2N1CCN(CC1)Cc1noc(c1)C)Br
InChI:
InChI=1S/C26H31BrN8O/c1-18-15-20(31-36-18)17-33-9-13-35(14-10-33)24-22(27)16-28-26-23(24)29-25(30-26)19-3-5-21(6-4-19)34-11-7-32(2)8-12-34/h3-6,15-16H,7-14,17H2,1-2H3,(H,28,29,30)
InChIKey:
GFLQCBTXTRCREJ-UHFFFAOYSA-N

Cite this record

CBID:73305 http://www.chembase.cn/molecule-73305.html

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NAMES AND DATABASE IDS

NAMES AND DATABASE IDS

Names Database IDs
IUPAC name
1-{6-bromo-2-[4-(4-methylpiperazin-1-yl)phenyl]-3H-imidazo[4,5-b]pyridin-7-yl}-4-[(5-methyl-1,2-oxazol-3-yl)methyl]piperazine
IUPAC Traditional name
1-{6-bromo-2-[4-(4-methylpiperazin-1-yl)phenyl]-3H-imidazo[4,5-b]pyridin-7-yl}-4-[(5-methyl-1,2-oxazol-3-yl)methyl]piperazine
Synonyms
CCT137690
CAS Number
1095382-05-0
PubChem SID
162038225
PubChem CID
25154041

DATA SOURCES

DATA SOURCES

All Sources Commercial Sources Non-commercial Sources
Data Source Data ID Price
Selleck Chemicals
S2744 external link Add to cart Please log in.
Data Source Data ID
PubChem 25154041 external link

CALCULATED PROPERTIES

CALCULATED PROPERTIES

JChem
Acid pKa 10.398801  H Acceptors
H Donor LogD (pH = 5.5) 0.9005442 
LogD (pH = 7.4) 2.9152305  Log P 3.483195 
Molar Refractivity 157.1281 cm3 Polarizability 55.67995 Å3
Polar Surface Area 80.56 Å2 Rotatable Bonds
Lipinski's Rule of Five false 

PROPERTIES

PROPERTIES

Safety Information Product Information Bioassay(PubChem)
Storage Condition
-20°C expand Show data source
Salt Data
Free Base expand Show data source

DETAILS

DETAILS

Selleck Chemicals Selleck Chemicals
Selleck Chemicals - S2744 external link
Research Area
Description Cancer
Biological Activity
Description CCT137690 is a highly selective inhibitor of Aurora A, Aurora B and Aurora C with IC50 of 15 nM, 25 nM and 19 nM, respectively.
Targets Aurora A Aurora B Aurora C
IC50 15 nM 25 nM 19 nM [1]
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, CCT137690 also inhibit the phosphorylation of histone H3. CCT137690 inhibits the major cytochrome P450 isoforms (CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP3A4) with IC50 greater than 10 μM. However, CCT137690 is a moderate inhibitor of the hERG ion-channel with IC50 of 3.0 μM. [1] CCT137690 effectively inhibits the growth of human tumor cell lines of different origins with GI50 ranging from 0.005 to 0.47 μM. CCT137690 completely inhibits both Aurora A autophosphorylation at T288 and histone H3 phosphorylation at 0.5 μM. CCT137690 induces polyploidy, mitotic aberrations, and apoptosis in HCT116 cells. CCT137690 reduces MYCN levels and GSK3β phosphorylation in the KELLY neuroblastoma cell line. [2] CCT137690 inhibits autophosphorylation of FLT3 and phosphorylation of its downstream targets STAT5 and p44/42 MAPK (Erk1/2).
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. [1] CCT137690 inhibits growth of MYCN-induced neuroblastoma at a dose of 100 mg/kg. [2] Additionally, CCT137690 achieves target modulation and potently inhibits the growth of subcutaneous MOLM-13 xenografts, with no obvious toxicity or loss of body weight. [3]
Clinical Trials
Features
Protocol
Kinase Assay [1]
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.
Cell Assay [1]
Cell Lines SW620, A2780 and HCT116 cells
Concentrations 0-50 μM
Incubation Time 72 hours
Methods The effects of CCT137690 on cell proliferation are analyzed with the colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cells such as SW620 and A2780 are plated in 96-well plates at 2.5 × 103 per well and are treated with a range of 0 to 50 μM of CCT137690 for 72 hours. The absorbance is measured at 570 nm using the Wallac VICTOR2TM 1420 Multilabel Counter.
Animal Study [1]
Animal Models Female CrTac:NCr-Fox1(nu) athymic mice bearing established SW620 human colorectal tumors
Formulation DMSO-Tween-saline
Doses 75 mg/kg
Administration Administered orally twice a day for 21 days
References
[1] Bavetsias V, et al. J Med Chem, 2010, 53(14), 5213-5228.
[2] Faisal A, et al. Mol Cancer Ther, 2011, 10(11), 2115-2123.
[3] Moore AS, et al. ASH Annu Meeting Abstr, 2010, 116, Abstr 3289.

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