<Suppliers Price>

CCT 137690

Names

[ CAS No. ]:
1095382-05-0

[ Name ]:
CCT 137690

[Synonym ]:
3-((4-(6-bromo-2-(4-(4-methylpiperazin-1-yl)phenyl)-3H-imidazo[4,5-b]pyridin-7-yl)piperazin-1-yl)methyl)-5-methylisoxazole
6-Bromo-7-{4-[(5-methyl-1,2-oxazol-3-yl)methyl]-1-piperazinyl}-2-[4-(4-methyl-1-piperazinyl)phenyl]-1H-imidazo[4,5-b]pyridine
cc-66
1H-Imidazo[4,5-b]pyridine, 6-bromo-7-[4-[(5-methyl-3-isoxazolyl)methyl]-1-piperazinyl]-2-[4-(4-methyl-1-piperazinyl)phenyl]-
CS-0706
CCT137690
CCT 137690

Biological Activity

[Description]:

CCT 137690 is a potent and orally available aurora kinase inhibitor with IC50s of 15, 25, and 19 nM for aurora A, B and C, respectively.

[Related Catalog]:

Research Areas >> Cancer

[Target]

Aurora A:15 nM (IC50)

Aurora B:25 nM (IC50)

Aurora C:19 nM (IC50)


[In Vitro]

CCT 137690 displays antiproliferative activity in a range of human tumor cell lines, including SW620 colon carcinoma (GI50=0.30 μM) and A2780 ovarian cancer cell line (GI50=0.14 μM). CCT 137690 inhibits in vitro phosphorylation of histone H3. CCT 137690 is a moderate inhibitor of the hERG ion-channel (IC50=3.0 μM)[1]. CCT137690 efficiently inhibits histone H3 and TACC3 phosphorylation (Aurora B and Aurora A substrates, respectively) in HCT116 and HeLa cells. Continuous exposure of tumour cells to the inhibitor causes multipolar spindle formation, chromosome misalignment, polyploidy and apoptosis[2].

[In Vivo]

CCT 137690 slows the growth of the SW620 xenografts with no observed toxicity[1]. CCT 137690 significantly inhibits tumour growth in a transgenic mouse model of neuroblastoma (TH-MYCN) that overexpresses MYCN protein and is predisposed to spontaneous neuroblastoma formation[2].

[Cell Assay]

Cells are plated in 96-well plates at 3,000 cells per well and are treated with a range of 0 to 25 mol/L of CCT137690 for 72 h. Cell proliferation assays are performed by colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)[2].

[Animal admin]

Mice: Animals are randomized into two groups, group 1: treatment with 100 mg/kg CCT137690 n=4 or group 2: vehicle control n=4. Treatment is administered via oral gavage twice daily. Tumour volumes are measured at day 0, 3 (48 hours after treatment started), 7 and 10 using 1H MRI[2].

[References]

[1]. Bavetsias V, et al. Imidazo[4,5-b]pyridine derivatives as inhibitors of Aurora kinases: lead optimization studies toward the identification of an orally bioavailable preclinical development candidate. J Med Chem. 2010 Jul 22;53(14):5213-28.

[2]. Faisal A, et al. The aurora kinase inhibitor CCT137690 downregulates MYCN and sensitizes MYCN-amplified neuroblastoma in vivo. Mol Cancer Ther. 2011 Nov;10(11):2115-23.


[Related Small Molecules]

Alisertib (MLN8237) | Tozasertib | AT9283 | Barasertib (AZD1152-HQPA) | danusertib | Hesperadin | Reversine | MLN8054 | GSK1070916 | AMG-900 | KW-2449 | TAK-632 | TAK-901 | MK-5108(VX-689) | pf-03814735

Chemical & Physical Properties

[ Density]:
1.4±0.1 g/cm3

[ Boiling Point ]:
722.9±70.0 °C at 760 mmHg

[ Molecular Formula ]:
C26H31BrN8O

[ Molecular Weight ]:
551.481

[ Flash Point ]:
391.0±35.7 °C

[ Exact Mass ]:
550.180420

[ PSA ]:
80.56000

[ LogP ]:
3.07

[ Vapour Pressure ]:
0.0±2.3 mmHg at 25°C

[ Index of Refraction ]:
1.664

[ Storage condition ]:
-20℃

Safety Information

[ RIDADR ]:
NONH for all modes of transport

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Related Compounds