BPTES

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Chemical Structure| 314045-39-1 同义名 : -
CAS号 : 314045-39-1
货号 : A413914
分子式 : C24H24N6O2S3
纯度 : 98%+
分子量 : 524.68
MDL号 : MFCD01079848
存储条件：

Pure form Sealed in dry, 2-8°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 : -
动物实验配方：
生物活性
靶点

  • glutaminase

    Glutaminase GLS1 (KGA), IC50:0.16 μM
描述 Glutaminase (GLS) is responsible for the hydrolysis of glutamine into glutamate and ammonia. BPTES is a potent and selective allosteric inhibitor of kidney-type GLS （KGS） with an IC50 value of 3.3 ± 0.7 μM[6]. In both WT and mutant IDH1 expressing cells, BPTES at 10 μM resulted in 59% and 68% inhibition, respectively, of glutaminase activity. The administration of BPTES also diminished the levels of glutamate and α-KG. However, the levels of glycolytic intermediates, incudling fructose-1,6-bisphosphate, dihydroxy-acetone-phosphate, and 3-phosphoglycerate, were increased by BPTES treatment[7]. In P493 cells, BPTES at 2 - 20 μM effectively suppressed cell proliferation under both aerobic and hypoxic conditions. When P493 cells were treated by 2 μM BPTES for 20h, the steady state ATP levels were significantly downregulated compared to control cells under both normoxia and hypoxia. The administration of tumor-bearing SCID mice with BPTES (12.5 mg/kg, once every other day) for 20 days significantly diminished tumor progression compared to DMSO-treated group[8].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.91mL

0.38mL

0.19mL

9.53mL

1.91mL

0.95mL

19.06mL

3.81mL

1.91mL
参考文献

[1]Xiang Y, Stine ZE, et al. Targeted inhibition of tumor-specific glutaminase diminishes cell-autonomous tumorigenesis. J Clin Invest. 2015 Jun;125(6):2293-306.

[2]Seltzer MJ, Bennett BD, et al. Inhibition of glutaminase preferentially slows growth of glioma cells with mutant IDH1. Cancer Res. 2010 Nov 15;70(22):8981-7.

[3]Lee JS, Kang JH, et al. Dual targeting of glutaminase 1 and thymidylate synthase elicits death synergistically in NSCLC. Cell Death Dis. 2016 Dec 8;7(12):e2511.

[4]Elgogary A, Xu Q, et al. Combination therapy with BPTES nanoparticles and metformin targets the metabolic heterogeneity of pancreatic cancer. Proc Natl Acad Sci U S A. 2016 Sep 6;113(36):E5328-36.

[5]Yeh TK, Kuo CC, et al. Design, Synthesis, and Evaluation of Thiazolidine-2,4-dione Derivatives as a Novel Class of Glutaminase Inhibitors. J Med Chem. 2017 Jul 13;60(13):5599-5612.

[6]Shukla K, Ferraris DV, Thomas AG, Stathis M, Duvall B, Delahanty G, Alt J, Rais R, Rojas C, Gao P, Xiang Y, Dang CV, Slusher BS, Tsukamoto T. Design, synthesis, and pharmacological evaluation of bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide 3 (BPTES) analogs as glutaminase inhibitors. J Med Chem. 2012 Dec 13;55(23):10551-63. doi: 10.1021/jm301191p. Epub 2012 Nov 30. PMID: 23151085; PMCID: PMC3539823.

[7]Seltzer MJ, Bennett BD, Joshi AD, Gao P, Thomas AG, Ferraris DV, Tsukamoto T, Rojas CJ, Slusher BS, Rabinowitz JD, Dang CV, Riggins GJ. Inhibition of glutaminase preferentially slows growth of glioma cells with mutant IDH1. Cancer Res. 2010 Nov 15;70(22):8981-7. doi: 10.1158/0008-5472.CAN-10-1666. Epub 2010 Nov 2. PMID: 21045145; PMCID: PMC3058858.

[8]Le A, Lane AN, Hamaker M, Bose S, Gouw A, Barbi J, Tsukamoto T, Rojas CJ, Slusher BS, Zhang H, Zimmerman LJ, Liebler DC, Slebos RJ, Lorkiewicz PK, Higashi RM, Fan TW, Dang CV. Glucose-independent glutamine metabolism via TCA cycling for proliferation and survival in B cells. Cell Metab. 2012 Jan 4;15(1):110-21. doi: 10.1016/j.cmet.2011.12.009. PMID: 22225880; PMCID: PMC3345194.