BPTES is a potent and selective allosteric inhibitor of kidney-type glutaminase (GLS) that has served as a molecular probe to determine the therapeutic potential of GLS inhibition[1].
In vitro, BPTES (2, 5 and 10μM) could effectively and specifically suppress NLRP1b inflammasome activation in macrophages[2]. BPTES (10μM; 6h) pretreatments increased the toxic effects of cisplatin and etoposide on HCC1937 and BT-549 cells[3]. BPTES (0, 0.05, 0.5, 1, 2.5 and 5μM; 72h) selectively eliminates human skin senescent fibroblasts[4]. BPTES (10μM; 24h) reduces Extracellular vesicle (EV) release in HIV-1-infected macrophages and immune-activated microglia[5].
In vivo, BPTES (1mg/kg; 1h; i.p.) can block the anthrax lethal toxin-induced mortality and tissue injury in mice by preventing injury to lungs, adrenal glands and intestine[2]. BPTES (0.25mg/20g/200μL; 2-3 times a week for 1 month; i.p.) can eliminate SA-β-Gal-positive cells in a human skin graft chimera model in mice[4].
References:
[1] Shukla K, Ferraris DV, Thomas AG, et al. 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.
[2] Wang J, Yang D, Shen X, et al. BPTES inhibits anthrax lethal toxin-induced inflammatory response. Int Immunopharmacol. 2020 Aug;85:106664.
[3] Chen L, Cui H, Fang J, et al. Glutamine deprivation plus BPTES alters etoposide- and cisplatin-induced apoptosis in triple negative breast cancer cells. Oncotarget. 2016 Aug 23;7(34):54691-54701.
[4] Takaya K, Ishii T, Asou T, et al. Glutaminase inhibitors rejuvenate human skin via clearance of senescent cells: a study using a mouse/human chimeric model. Aging (Albany NY). 2022 Nov 21;14(22):8914-8926.
[5] Wu B, Liu J, Zhao R, et al. Glutaminase 1 regulates the release of extracellular vesicles during neuroinflammation through key metabolic intermediate alpha-ketoglutarate. J Neuroinflammation. 2018 Mar 14;15(1):79.