半岛bd体育手机客户端 说明
一般描述
A cell-permeable benzothiazolylchromenone compound that disrupts Skp2-Skp1 interaction via direct Skp2 affinity binding and selectively prevents Skp2-, but not Fbw7- or β-TrCP-, Skp1-Cullin-1-F-box (SFC) complex-mediated substrates ubiquitination both in cell-free systems and in cultures, effectively preventing ubiquitination-dependent activation (Akt) and degradation (p21 & p27) of Skp2 substrates with concomitant down-regulation of cellular Skp2 protein level (10 to 20 ?M in HEK293T & PC3 cultures). Exhibits antiproliferation activity toward a panel of 8 cancer (IC50from 1.22 to 10.5 ?M), but not normal PNT1A epithelial or IMR90 fibroblast, lines and effectively reduces ALDH+cancer stem cell (CSC; Cancer Initiating Cell) population in prostate cancer PC3 cultures (10 to 20 ?M) by promoting p53-independent senescence and blocking Akt-dependent aerobic glycolysis. Exhibits good pharmacokinetic property (tmax= 1 h;t1/2>6 h;Cmax>1 ?M/plasma and >4 ?M/tumor in 200 mm3PC3 tumor-bearing mice; 80 mg/kg i.p.) and is efficacious in suppressing A549 and PC3 tumor growth in mice (40 to 80 mg/kg/d i.p.)in vivo.
A cell-permeable benzothiazolylchromenone compound that disrupts Skp2-Skp1 interaction via direct Skp2 affinity binding and selectively prevents Skp2-, but not Fbw7- or β-TrCP-, Skp1-Cullin-1-F-box (SFC) complex-mediated substrates ubiquitination, effectively preventing Skp2 substrates activation (Akt) and degradation (p21 & p27) with concomitant down-regulation of cellular Skp2 protein level (10 to 20 ?M in HEK293T & PC3 cultures). Exhibits antiproliferation activity toward a panel of 8 cancer (IC50from 1.22 to 10.5 ?M) and reduces ALDH+cancer stem cell population in PC3 cultures (10 to 20 ?M). Exhibits good pharmacokinetic property and is efficacious in suppressing A549 and PC3 tumor growth in mice (40 to 80 mg/kg/d i.p.)in vivo.
生化/生理作用
Cell permeable: yes
Primary Target
Skp2
Reversible: yes
包装
Packaged under inert gas
警告
Toxicity: Standard Handling (A)
重悬
Use only fresh DMSO for reconstitution.
其他说明
Chan, C.H., et al. 2013Cell154,556.
法律信息
CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany
基本信息
经验(实验)分子式 | C24H24N2O3S |
分子量 | 420.52 |
半岛bd体育手机客户端 性质
质量水平 | 100 |
测定 | ≥98% (HPLC) |
形式 | powder |
manufacturer/tradename | Calbiochem? |
储存条件 | OK to freeze protect from light |
颜色 | beige |
溶解性 | DMSO: 5 mg/mL |
储存温度 | 2-8℃ |
安全信息
储存分类代码 | 11 - Combustible Solids |
WGK | WGK 3 |
闪点(F) | Not applicable |
闪点(C) | Not applicable |
Sigma-Aldrich