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CCT129202

产品号 S1519 公司名称 Selleck Chemicals
CAS号 942947-93-5 公司网站 http://www.selleckchem.com
分子式 C23H25ClN8OS 电 话 (877) 796-6397
分子量 497.0156 传 真 (832) 582-8590
纯 度 电子邮件 sales@selleckchem.com
保 存 -20°C Chembase数据库ID: 72720

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产品别名

标题
CCT129202
IUPAC标准名
2-(4-{6-chloro-2-[4-(dimethylamino)phenyl]-3H-imidazo[4,5-b]pyridin-7-yl}piperazin-1-yl)-N-(1,3-thiazol-2-yl)acetamide
IUPAC传统名
2-(4-{6-chloro-2-[4-(dimethylamino)phenyl]-3H-imidazo[4,5-b]pyridin-7-yl}piperazin-1-yl)-N-(1,3-thiazol-2-yl)acetamide

产品登记号

CAS号 942947-93-5

产品性质

作用靶点 Aurora kinase
成盐信息 Free Base
保存条件 -20°C

产品详细信息

详细说明 (English)
Research Area
Description Cancer
Biological Activity
Description CCT129202 is an ATP-competitive pan-Aurora inhibitor for Aurora A, Aurora B and Aurora C with IC50 of 0.042 μM, 0.198 μM and 0.227 μM, respectively.
Targets Aurora A Aurora B Aurora C
IC50 0.042 μM 0.198 μM 0.227 μM [1]
In Vitro CCT129202 is an ATP-competitive inhibitor of recombinant Aurora A kinase with a Ki of 49.8 nM. CCT129202 at 1 μM shows high selectivity for Aurora A and Aurora B with 92% and 60% inhibition, respectively. It inhibits FGFR3 slightly by 27%, and is not active against CRAF. CCT129202 inhibits proliferation in multiple cultures of human tumor cell lines with half-maximal growth inhibition (GI50) values ranging from 0.08 μM for MV4-11 to 1.7 μM for MDA-MB-157. The effects are in association with increased expression levels of Aurora A and Aurora B leading to aberrant mitosis. Treatment with CCT129202 (0.7 μM) causes the accumulation of HCT116 cells with ≥4N DNA content, leading to apoptosis in a time dependent manner. Application of CCT129202 in HCT116 cells causes decreased histone H3 phosphorylation and increased p53 protein stabilization, which are consistent with the inhibition of Aurora B and Aurora A, respectively. CCT129202 induces up-regulation of p21 in HCT116, HT29 and Hela cells in a p53 dependent and independent manner, which leads to decreased phosphorylation of the Rb protein and activity of E2F in a concentration-dependent manner. [1]
In Vivo Administration of CCT129202 at 100 mg/kg in athymic mice bearing s.c. HCT116 colon cancer xenografts causes ~50% reduction of histone H3 phosphorylation after 30 minutes of treatment, and significantly inhibits tumor growth by 57.7% compared to control mice after a period of 9 days of treatment. [1]
Clinical Trials
Features
Protocol
Kinase Assay [1]
Inhibition of Aurora Kinases NH2-terminal glutathione S-transferase (GST)-fusion recombinant human Aurora A (aa 118-403), Aurora B (full length), and Aurora C (full length) are expressed in baculovirus, purified, and used in the kinase inhibition assays. The in vitro kinase assays are performed in kinase buffer (50 mM Tris pH 7.5, 10 mM NaCl, 2.5 mM MgCl2 and 1 mM DTT) containing γ-32P-ATP, Aurora kinase and different concentrations of CCT129202. The reactions are incubated for 30 minutes at 30 °C and stopped by adding sample buffer. The reactions are separated on Novex Tris-Glycine gels and dried on a vacuum gel drier at 80 °C for 1 hour before exposure to Kodak-Biomax XR film. The concentration of CCT129202 that inhibits Aurora kinases by 50% is calculated representing IC50 value.
Cell Assay [1]
Cell Lines Colo205, SW620, HCT116, HT29, KW12, Hela, A2780, OVCAR8, MDA-MB-157 and MV4-11 cell lines
Concentrations Dissolved in DMSO, final concentration ~50 μM
Incubation Time 72 hours
Methods Cells are treated with a range of 0 to 50 uM of CCT129202 for 72 hours. Cell proliferation is analyzed with the colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The absorbance is measured at 570 nm using the Wallac VICTOR2TM 1420 Multilabel Counter.
Animal Study [1]
Animal Models HCT116 colon carcinoma is established in female NCr athymic mice.
Formulation Dissolved in 10% DMSO, 5% Tween 20 in saline
Doses ~100 mg/kg
Administration Injection i.p
References
[1] Chan F, et al. Mol Cancer Ther. 2007, 6(12), 3147-3157.