BPTES (CAS: 314045-39-1)

C₂₄H₂₄N₆O₂S₃

• Selective, allosteric non-competitive inhibitor of glutaminase 1 (GLS1), selective for GLS1 over GLS2, glutamate dehydrogenase, and γ-glutamyl transpeptidase, consequently inhibiting glutaminolysis.
• Useful agent for immunometabolism research. Glutaminase converts glutamine to glutamate, which is an important excitatory neurotransmitter in brain and can be further oxidized to α-ketoglutarate to feed the tricarboxylic acid (TCA) cycle and to glutathione, which is important for controlling the level of reactive oxygen species (ROS), particularly important for cancer cell growth.
• Anticancer agent. Increases the production of reactive oxygen species and reduces ATP levels in hypoxic cells, induces cell death of P493 human lymphoma B cells in vitro and delays tumor xenograft growth in vivo.

1. Novel mechanism of inhibition of rat kidney-type glutaminase by bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide (BPTES): M.M. Robinson, et al.; Biochem. J. 406, 407 (2007)
2. Inhibition of glutaminase preferentially slows growth of glioma cells with mutant IDH1: M.J. Seltzer, et al.; Cancer Res. 70, 8981 (2010)
3. Full-length human glutaminase in complex with an allosteric inhibitor: B. DeLaBarre, et al.; Biochemistry 50, 10764 (2011)
4. BPTES inhibition of hGA(124-551), a truncated form of human kidney-type glutaminase: E.W. Hartwick & N.P. Curthoys; J. Enzyme Inhib. Med. Chem. 27, 861 (2012)
5. Glucose-independent glutamine metabolism via TCA cycling for proliferation and survival in B cells: A. Le, et al.; Cell Metab. 15, 110 (2012)
6. Design, synthesis, and pharmacological evaluation of bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide 3 (BPTES) analogs as glutaminase inhibitors: K. Shukla, et al.; J. Med. Chem. 55, 10551 (2012)
7. Availability of the key metabolic substrates dictates the respiratory response of cancer cells to the mitochondrial uncoupling: A.V. Zhdanov, et al.; Biochim. Biophys. Acta 1837, 51 (2014)
8. Small molecule glutaminase inhibitors block glutamate release from stimulated microglia: A.G. Thomas, et al.; BBRC 443, 32 (2014)
9. Targeted inhibition of tumor-specific glutaminase diminishes cell-autonomous tumorigenesis: Y. Xiang, et al.; J. Clin. Invest. 125, 2293 (2015)
10. Design and evaluation of novel glutaminase inhibitors: L.A. McDermott, et al.; Bioorg. Med. Chem. 24, 1819 (2016)
11. Glutaminase 1 inhibition reduces thymidine synthesis in NSCLC: J.S. Lee, et al.; BBRC 477, 374 (2016)
12. Inhibition of Glutaminolysis Inhibits Cell Growth via Down-regulating Mtorc1 Signaling in Lung Squamous Cell Carcinoma: X. Ye, et al.; Anticancer Res. 36, 6021 (2016)
13. A guide to immunometabolism for immunologists: L.A. O'Neill, et al.; Nat. Rev. Immunol. 16, 553 (2016) (Review)
14. Characterization of the interactions of potent allosteric inhibitors with glutaminase C, a key enzyme in cancer cell glutamine metabolism: Q. Huang, et al.; J. Biol. Chem. 293, 3535 (2018)