Glutaminase Inhibitor II, BPTES

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.).

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.

Cell permeable: yes

Primary Target
kidney-type glutaminase

Reversible: yes

Target IC₅₀: 140 and 210 nM in HEK293 cells expressing wt-KGA and F318Y-cKGA, respectively

Packaged under inert gas

Toxicity: Standard Handling (A)

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.

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Robinson, M.M., et al. 2007. Biochem. J.406, 407.

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany