产品说明
一般描述
A cell-permeable bis-thiadiazole compound that selectively inhibits GLS1 (IC50 = 60 and 80 nM, respectively, against hKGA and hGAC), but not the liver-type GLS2/LGA (IC50 = 88 µM using hLGA), mitochondrial glutaminase (GA) activity by inducing an inactive GLS1 tetrameric conformation via a 2:1 inhibitor-to-tetramer stoichiometric binding, non-competitive against glutamine or phosphate binding. B-cell lymphoma line P493 is shown to depend primarily on glutamine metabolism for survival under hypoxic condition and cellular GLS1 inhibtion by BPTES treatment results in cell death (2 µM BPTES & 3% O2 for 4 d), while under aerobic/normoxic condition (20% O2 and up to 10 µM BPTES for 4 d) only growth inhibition is observed. Likewise, intraperitoneal administration (12.5 mg/kg or 200 µg/animal; q.o.d.) is demonstrated to be efficacious in suppressing P493 tumor expansion in mice in vivo.
A cell-permeable bis-thiadiazole compound that selectively inhibits GLS1 (IC50 = 60 and 80 nM, respectively, against hKGA and hGAC), but not the liver-type GLS2/LGA (IC50 = 88 µM using hLGA) mitochondrial glutaminase (GA) activity by inducing an inactive GLS1 tetrameric conformation via a 2:1 inhibitor-to-tetramer stoichiometric binding. Shown to induce growth inhibition under aerobic/normoxic (up to 10 µM; 20% O2) and cell death under hypoxic (2 µM; 3% O2) in P493 B-cell lymphoma cultures in vitro and effectively suppress P493 tumor expansion in mice in vivo (12.5 mg/kg or 200 µg/animal via i.p.; q.o.d.).
生化/生理作用
Cell permeable: yes
Target IC50: 140 and 210 nM in HEK293 cells expressing wt-KGA and F318Y-cKGA, respectively
Primary Target
kidney-type glutaminase
Reversible: yes
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
Shukla, K., et al. 2012. J. Med. Chem.55, 10551.
Thangavelu, K., et al. 2012. Proc. Natl. Acad. Sci. USA109, 7705.
Le, A., et al. 2012. Cell Metab.15, 110.
DeLaBarre, B., et al. 2011. Biochemistry 50, 10764.
Seltzer, M.J., et al. 2010. Cancer Res.70, 8981.
Robinson, M.M., et al. 2007. Biochem. J.406, 407.
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 | C24H24N6O2S3 |
| 分子量 | 524.68 |
| MDL编号 | MFCD01079848 |
产品性质
| 质量水平 | 100 |
| 测定 | ≥94% (HPLC) |
| 形式 | powder |
| manufacturer/tradename | Calbiochem® |
| 储存条件 | OK to freeze protect from light |
| 颜色 | yellow |
| 溶解性 | DMSO: 50 mg/mL |
| 储存温度 | −20℃ |
安全信息
| 象形图 |  |
| 警示用语： | Warning |
| 危险声明 | H315 - H319 - H335 |
| 预防措施声明 | P261 - P264 - P271 - P280 - P302 + P352 - P305 + P351 + P338 |
| 危险分类 | Eye Irrit. 2 - Skin Irrit. 2 - STOT SE 3 |
| 靶器官 | Respiratory system |
| 储存分类代码 | 11 - Combustible Solids |
| WGK | WGK 3 |
| 闪点(F) | Not applicable |
| 闪点(C) | Not applicable |
Sigma-Aldrich
m.cnreagent.com
