您好,欢迎来到化工原料网! [登录] [免费注册]
化工原料网
位置:首页 > 产品库 > K858
立即咨询
咨询类型:
     
*姓名:
*电话:
*单位:
Email:
*留言内容:
请详细说明您的需求。
*验证码:
 
K858
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
K858图片
CAS NO:72926-24-0
规格:≥98%
包装与价格:
包装价格(元)
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
250mg电议
500mg电议
1g电议

产品介绍
理化性质和储存条件
Molecular Weight (MW) 277.34
Formula C13H15N3O2S
CAS No. 72926-24-0
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: 10 mM in DMSO
Water: <1 mg/mL
Ethanol:
SMILES Code CC(NC1=NN(C(C)=O)C(C2=CC=CC=C2)(C)S1)=O
Synonyms K-858; K 858; K858.
实验参考方法
In Vitro

In vitro activity: K-858 is a novel, potent and ATP-uncompetitive inhibitor of mitotic kinesin Eg5 that has potential antitumor activity. K858 is a potent inhibitor of replication and induces apoptosis in breast tumor cells, independently from the tumor phenotype. This anti-proliferative response of tumor cells to K858 can be limited by the contemporaneous over-expression of survivin; consequently, the reduction of survivin levels, obtained with AKT inhibitors, can sensitize tumor cells to K858-induced apoptosis. K858 blocked centrosome separation, activated the spindle checkpoint, and induced mitotic arrest in cells accompanied by the formation of monopolar spindles. K858 induces mitotic arrest and growth inhibition through the activation of the Mad2-mediated spindle checkpoint. K858 induces mitotic cell death in cancer cells but not in normal cells. K858 induces mitotic arrest, apoptosis, and cell growth inhibition and has no effect on microtubule polymerization.


Kinase Assay: K858 is an ATP-uncompetitive inhibitor of Eg5 that is at least 150-fold more selective for Eg5 than other members of the kinesin superfamily. K858 induces mitotic arrest and growth inhibition through the activation of the Mad2-mediated spindle checkpoint. K858 induces mitotic cell death in cancer cells but not in normal cells. K858 induces mitotic arrest, apoptosis, and cell growth inhibition and has no effect on microtubule polymerization.


Cell Assay: To determine cytotoxicity, sulforhodamine B colorimetric assay is performed: 1.5 × 104 cells are plated on 96 well plates, grown for 24 h and treated with different concentrations of K858 (1 μM, 10 μM, 100 μM) for 24 and 48 h. Cells are then fixed with 50 % trichloroacetic acid for 1 h at 4°C and stained for 30 min at room temperature (RT) with 0.4 % sulforhodamine B in 1 % acetic acid. Excess dye is removed by washing four times with 1 % acetic acid. Protein bound dye is dissolved in 10 mM TRIS pH 10, and optical density (OD) is determined at 510 nm using a microplate reader.

In VivoK858 exhibits antitumor activity and induces mitotic arrest in a human tumor xenograft mouse model. K858 (50, 150 mg/kg, p.o.) shows antitumor activity in an A2780 ovarian cancer xenograft model, also inhibits tumor grwoth in a HCT116 colon cancer xenograft model via 100 mg/kg twice a day orally for 5 days. K858 (100 mg/kg, p.o., qd ×5) displays no neurotoxic side effects in mice
Animal model Mouse with A2780 ovarian cancer xenograft model
Formulation & Dosage 50, 150 mg/kg, p.o.
References Biochem Pharmacol. 2013 Nov 15;86(10):1441-51.Biochem Pharmacol. 2013 Nov 15;86(10):1441-51.