Glutaminase Inhibitor II, BPTES-CAS 314045-39-1-Calbiochem

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

产品性质

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