半岛bd体育手机客户端 说明
一般描述
A cell-permeable imidazopyrimidinyl-thiazolamine compound that effectively downregulates cellular BMI-1 protein level both in culturesin vitro(IC50= 0.5 ?M/48 h/HT1080 and <0.37 ?M/HCT116/overnight) and in micein vivo(60 mg/kg/d via s.c.) by inhibiting BMI-1 transcription via a yet unidentified mechanism, thereby reducing BMI-1-dependent RING1A E3 ligase activity and RING1A-mediated H2A ubiquitination (uH2A)/epigenetic regulations. Shown to exhibit antiproliferation activity against human colon cancer cells both in cultures (IC50<300 nM)in vitroand in mice (30 to 60 mg/kg/d s.c.)in vivovia G0 cell cycle arrest and apoptosis induction with a greater drug impact on self-renewing cancer-initiating cells (CICs; cancer stem cells).
A cell-permeable imidazopyrimidinyl-thiazolamine compound that effectively downregulates cellular BMI-1 protein level both in culturesin vitro(IC50= 0.5 ?M/48 h/HT1080 and <0.37 ?M/HCT116/overnight) and in micein vivo(4.5 ng vs.13.7 ng per mg HT1080 tumor tissue, respectively, with or without 10-d 60 mg/kg/d treatment via s.c.) by inhibiting BMI-1 transcription (IC50= 0.5 ?M against overnight reporter transcription in HEK293) via a yet unidentified mechanism, thereby reducing BMI-1-dependent RING1A E3 ligase activity and RING1A-mediated H2A ubiquitination (uH2A)/epigenetic regulations. Shown to exhibit antiproliferation activity against human colon cancer cells both in cultures (IC50<300 nM against LS174T and primary colon cancer cultures)in vitroand in mice (30 to 60 mg/kg/d s.c.)in vivoby inducing cell cycle arrest at G0and apoptosis. Reduced frequency of sphere-forming cells is observed among surviving cells (by 1.7- to 2.2-fold) upon PTC-209 removal post a 4-day 0.1 ?M drug treatment period in primary colon cancer cultures, indicating a greater impact of drug treatment on self-renewing cancer-initiating cells (CICs; cancer stem cells). Likewise, surviving colon cancer cells from tumor-bearing mice at the end of drug treatment are shown to contain reduced population of tumor-initiating cells when xenografted into secondary recipient mice.
生化/生理作用
Cell permeable: yes
Reversible: no
包装
Packaged under inert gas
警告
Toxicity: Standard Handling (A)
重悬
Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.
其他说明
Kreso, A., et al. 2014.Nat. Med.20,29.
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 | C17H13Br2N5OS |
分子量 | 495.19 |
MDL编号 | MFCD02110649 |
半岛bd体育手机客户端 性质
质量水平 | 100 |
测定 | ≥95% (HPLC) |
形式 | powder |
manufacturer/tradename | Calbiochem? |
储存条件 | OK to freeze protect from light |
颜色 | light yellow |
溶解性 | DMSO: 100 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