Description
BPTES (314045-39-1) is a potent and selective allosteric1 inhibitor of kidney-type glutaminase (GLS1), IC50 = 3.3 μM2.? Selective for GLS1 over GLS2, g-glutamyl transpeptidase and glutamate dehydrogenase. Shuts down an alternative energy-generating glutaminolysis pathway in P493 cells under both glucose deprivation or hypoxia.3 Reduces the growth of P493 cell xenografts by 50% over a 10 day treatment.4 BPTES inhibition of glutamine utilization in cancer cells increases PD-L1 expression.5 Clears senescent cells and improves various age-related disorders in a geriatric mouse model.6
Uses
Bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide (BPTES) has been used as a glutaminase inhibitor.
Biochem/physiol Actions
Vaccinia virus (VACV) requires glutamine metabolism for its optimal replication. Inhibition of glutaminolysis by bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide (BPTES) can be a potential method to treat poxvirus infections.
References
DeLaBarre et al. (2011), Full-length human glutaminase in complex with an allosteric inhibitor; Biochemistry 50 10764
Shukla et al. (2012), 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., 55 10551
Le et al. (2012), Glucose-independent glutamine metabolism via TCA cycling for proliferation and survival in B cells; Cell Metab. 15 110
Xiang et al. (2015), Targeted inhibition of tumor-specific glutaminase diminishes cell-autonomous tumorigenesis; J. Clin. Invest. 125 2293
Byun et al. (2020), Inhibition of Glutamine Utilization Synergizes with Immune Checkpoint Inhibitor to Promote Antitumor Immunity; Mol. Cell 80 592
Pan and Locasale (2021), Targeting metabolism to influence aging; Science 371 234
