CCT137690

製品コードS2744 バッチS274402

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C26H31BrN8O
分子量 551.48 CAS No. 1095382-05-0
Solubility (25°C)* 体外 DMSO 4 mg/mL (7.25 mM)
Water Insoluble
Ethanol Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 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.
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]

プロトコル(参考用のみ)

キナーゼアッセイ 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.
細胞アッセイ 細胞株 SW620, A2780 and HCT116 cells
濃度 0-50 μM
反応時間 72 hours
実験の流れ 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.
動物実験 動物モデル Female CrTac:NCr-Fox1(nu) athymic mice bearing established SW620 human colorectal tumors
投薬量 75 mg/kg
投与方法 Administered orally twice a day for 21 days

カスタマーフィードバック

, , Dr. Antonino Maria Sparta, University of Bologna

, , Dr. Antonino Maria Sparta, PhD University of Bologna

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

DELs enable the development of BRET probes for target engagement studies in cells [ Cell Chem Biol, 2023, 30(8):987-998.e24] PubMed: 37490918
RAE1 promotes nitrosamine-induced malignant transformation of human esophageal epithelial cells through PPARα-mediated lipid metabolism [ Ecotoxicol Environ Saf, 2023, 265:115513] PubMed: 37774541
Selective Impact of ALK and MELK Inhibition on ERα Stability and Cell Proliferation in Cell Lines Representing Distinct Molecular Phenotypes of Breast Cancer [ bioRxiv, 2023, 10.1101/2023.12.19.572304] PubMed: none
Induction of autophagy-dependent ferroptosis to eliminate drug-tolerant human retinoblastoma cells [ Cell Death Dis, 2022, 13(6):521] PubMed: 35654783
Lysophosphatidic acid suppresses apoptosis of high-grade serous ovarian cancer cells by inducing autophagy activity and promotes cell-cycle progression via EGFR-PI3K/Aurora-AThr288-geminin dual signaling pathways [ Front Pharmacol, 2022, 13:1046269] PubMed: 36601056
Targeting Aurora B kinase prevents and overcomes resistance to EGFR inhibitors in lung cancer by enhancing BIM- and PUMA-mediated apoptosis [ Cancer Cell, 2021, S1535-6108(21)00383-4] PubMed: 34388376
DCN released from ferroptotic cells ignites AGER-dependent immune responses [ Autophagy, 2021, 10.1080/15548627.2021.2008692] PubMed: 34964698
Trypsin-Mediated Sensitization to Ferroptosis Increases the Severity of Pancreatitis in Mice [ Cell Mol Gastroenterol Hepatol, 2021, S2352-345X(21)00196-X] PubMed: 34562639
Targeting NF-κB-dependent alkaliptosis for the treatment of venetoclax-resistant acute myeloid leukemia cells [ Biochem Biophys Res Commun, 2021, 562:55-61] PubMed: 34034094
A Human Organoid Model of Aggressive Hepatoblastoma for Disease Modeling and Drug Testing [ Cancers (Basel), 2020, 12(9)E2668] PubMed: 32962010

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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