BPTES | Glutaminase GLS1 inhibitor

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

References/Citations:

1. DeLaBarre et al. (2011), Full-length human glutaminase in complex with an allosteric inhibitor; Biochemistry 50 10764
2. 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
3. Le et al. (2012), Glucose-independent glutamine metabolism via TCA cycling for proliferation and survival in B cells; Cell Metab. 15 110
4. Xiang et al. (2015), Targeted inhibition of tumor-specific glutaminase diminishes cell-autonomous tumorigenesis; J. Clin. Invest. 125 2293
5. Byun et al. (2020), Inhibition of Glutamine Utilization Synergizes with Immune Checkpoint Inhibitor to Promote Antitumor Immunity; Mol. Cell 80 592
6. Pan and Locasale (2021), Targeting metabolism to influence aging; Science 371 234