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MedKoo Cat#: 407294 | Name: BPTES
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

BPTES is a selective inhibitor of Glutaminase GLS1 (KGA), which is found in the kidney and brain, and is positively regulated by myc and strongly expressed in many tumors and tumor cell lines. BPTES has a K(i) of approx. 3 microM. BPTES inhibits the allosteric activation caused by phosphate binding and promotes the formation of an inactive complex.

Chemical Structure

BPTES
BPTES
CAS#314045-39-1

Theoretical Analysis

MedKoo Cat#: 407294

Name: BPTES

CAS#: 314045-39-1

Chemical Formula: C24H24N6O2S3

Exact Mass: 524.1123

Molecular Weight: 524.68

Elemental Analysis: C, 54.94; H, 4.61; N, 16.02; O, 6.10; S, 18.33

Price and Availability

Size Price Availability Quantity
25mg USD 90.00 Ready to ship
50mg USD 150.00 Ready to ship
100mg USD 250.00 Ready to ship
200mg USD 450.00 Ready to ship
500mg USD 850.00 Ready to ship
1g USD 1,350.00 Ready to ship
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Related CAS #
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Synonym
BPTES
IUPAC/Chemical Name
N,N'-((thiobis(ethane-2,1-diyl))bis(1,3,4-thiadiazole-5,2-diyl))bis(2-phenylacetamide)
InChi Key
MDJIPXYRSZHCFS-UHFFFAOYSA-N
InChi Code
InChI=1S/C24H24N6O2S3/c31-19(15-17-7-3-1-4-8-17)25-23-29-27-21(34-23)11-13-33-14-12-22-28-30-24(35-22)26-20(32)16-18-9-5-2-6-10-18/h1-10H,11-16H2,(H,25,29,31)(H,26,30,32)
SMILES Code
O=C(NC1=NN=C(CCSCCC2=NN=C(NC(CC3=CC=CC=C3)=O)S2)S1)CC4=CC=CC=C4
Appearance
Solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Biological target:
BPTES is an allosteric and selective glutaminase inhibitor with an IC50 of 0.16 μM.
In vitro activity:
This study focused on investigating the effects of BPTES on the metabolism in several breast cancer cell lines using a combination of 1D and isotope tagged 2D NMR-based metabolomics approaches to visualize the altered metabolite profiles BPTES exhibited significant effects on the metabolite profiles of all three cell types. BPTES altered 14 metabolite levels significantly for MCF7 cells (p < 0.05; 4 upregulated; 10 downregulated) under hypoxia, while only one was altered significantly (p < 0.05, upregulated) under normoxia. On the other hand, BPTES altered 7 metabolite levels significantly for MDA-MB231 cells (p < 0.05; 2 upregulated; 5 downregulated) under hypoxia, while only two metabolites were altered significantly (p < 0.05; 2 upregulated) under normoxia. BPTES induced up to 2-fold changes in metabolite levels (Table1). For the non-cancerous cells, the response to BPTES was quite different; BPTES affected both normoxia and hypoxia cells significantly, albeit differently. For example, 7 metabolite levels were altered significantly (p < 0.05; 4 upregulated; 3 downregulated) under hypoxia, while under normoxia 10 metabolites were altered significantly (p < 0.05; 4 upregulated and 6 downregulated) (Figure2;Table11). BPTES significantly affected the glycolysis pathway for both the cancer cell types under hypoxia (Figure3). Specifically, BPTES caused a significant reduction in glucose and increase in lactate levels for MCF7 cells, while the effect was opposite for MDA-MB231 cells. BPTES also affected a number of metabolites associated with the TCA cycle (Figure4). In particular, it increased the levels of citrate for both MCF7 and MDA-MB231; however, the increase was significant (p < 0.05) only for MDA-MB231 cells. The distinct metabolic responses to BPTES treatment determined in the two breast cancer cell lines offer valuable metabolic information for the exploration of the therapeutic responses to breast cancer. Reference: Front Mol Biosci. 2018; 5: 49. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5962734/
In vivo activity:
BPTES was tested in vivo in an aggressive MYC-induced liver cancer model by activating MYC at birth, which normally results in the death of all animals by 11 weeks of age. The mice were treated with BPTES or vehicle at 3 weeks after birth because early tumor formation and increased GLS expression were evident by this time (Figure 1, C and E). Vehicle DMSO–treated LAP/MYC mice showed a median survival of approximately 7 weeks (n = 15) (Figure 3C). Remarkably, BPTES-treated LAP/MYC mice (n = 14) survived significantly longer than control mice, with a median survival of 11 weeks (P < 0.0001, Figure 3C). To gain insight into the in vivo biological effects of BPTES, its effects on glutamine and glutamate levels in tumors as well as its effects on proliferation were studied, as determined by Ki-67 staining. It was readily noted that the livers from the BPTES-treated mice were smaller than those from the control-treated mice, and importantly, there were fewer and smaller tumor nodules (Supplemental Figure 4, A and B) To determine the effect of BPTES treatment on glutaminase-mediated conversion of glutamine to glutamate in vivo, metabolites were extracted from liver tumors or the littermates’ normal livers. As expected, control DMSO–treated tumors had relatively higher levels of glutamate and lower levels of glutamine as compared with levels in BPTES-treated tumors, indicating that inhibition of GLS resulted in the accumulation of glutamine (P = 0.004, Figure 3E). Normal livers from littermate mice did not show a differential effect of BPTES versus DMSO on glutamine and glutamate levels. Therefore, normal liver tissues are largely dependent on normal hepatocyte GLS2, which is not inhibited by BPTES. Reference: J Clin Invest. 2015 Jun 1; 125(6): 2293–2306. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4497742/
Solvent mg/mL mM
Solubility
DMSO 58.0 110.66
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 524.68 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
1. Nagana Gowda GA, Barding GA Jr, Dai J, Gu H, Margineantu DH, Hockenbery DM, Raftery D. A Metabolomics Study of BPTES Altered Metabolism in Human Breast Cancer Cell Lines. Front Mol Biosci. 2018 May 15;5:49. doi: 10.3389/fmolb.2018.00049. PMID: 29868609; PMCID: PMC5962734. 2. Xiang Y, Stine ZE, Xia J, Lu Y, O'Connor RS, Altman BJ, Hsieh AL, Gouw AM, Thomas AG, Gao P, Sun L, Song L, Yan B, Slusher BS, Zhuo J, Ooi LL, Lee CG, Mancuso A, McCallion AS, Le A, Milone MC, Rayport S, Felsher DW, Dang CV. Targeted inhibition of tumor-specific glutaminase diminishes cell-autonomous tumorigenesis. J Clin Invest. 2015 Jun;125(6):2293-306. doi: 10.1172/JCI75836. Epub 2015 Apr 27. PMID: 25915584; PMCID: PMC4497742. 3. Kono M, Yoshida N, Maeda K, Suárez-Fueyo A, Kyttaris VC, Tsokos GC. Glutaminase 1 Inhibition Reduces Glycolysis and Ameliorates Lupus-like Disease in MRL/lpr Mice and Experimental Autoimmune Encephalomyelitis. Arthritis Rheumatol. 2019 Nov;71(11):1869-1878. doi: 10.1002/art.41019. Epub 2019 Sep 27. PMID: 31233276; PMCID: PMC6817384.
In vitro protocol:
1. Nagana Gowda GA, Barding GA Jr, Dai J, Gu H, Margineantu DH, Hockenbery DM, Raftery D. A Metabolomics Study of BPTES Altered Metabolism in Human Breast Cancer Cell Lines. Front Mol Biosci. 2018 May 15;5:49. doi: 10.3389/fmolb.2018.00049. PMID: 29868609; PMCID: PMC5962734. 2. Xiang Y, Stine ZE, Xia J, Lu Y, O'Connor RS, Altman BJ, Hsieh AL, Gouw AM, Thomas AG, Gao P, Sun L, Song L, Yan B, Slusher BS, Zhuo J, Ooi LL, Lee CG, Mancuso A, McCallion AS, Le A, Milone MC, Rayport S, Felsher DW, Dang CV. Targeted inhibition of tumor-specific glutaminase diminishes cell-autonomous tumorigenesis. J Clin Invest. 2015 Jun;125(6):2293-306. doi: 10.1172/JCI75836. Epub 2015 Apr 27. PMID: 25915584; PMCID: PMC4497742.
In vivo protocol:
1. Kono M, Yoshida N, Maeda K, Suárez-Fueyo A, Kyttaris VC, Tsokos GC. Glutaminase 1 Inhibition Reduces Glycolysis and Ameliorates Lupus-like Disease in MRL/lpr Mice and Experimental Autoimmune Encephalomyelitis. Arthritis Rheumatol. 2019 Nov;71(11):1869-1878. doi: 10.1002/art.41019. Epub 2019 Sep 27. PMID: 31233276; PMCID: PMC6817384. 2. Xiang Y, Stine ZE, Xia J, Lu Y, O'Connor RS, Altman BJ, Hsieh AL, Gouw AM, Thomas AG, Gao P, Sun L, Song L, Yan B, Slusher BS, Zhuo J, Ooi LL, Lee CG, Mancuso A, McCallion AS, Le A, Milone MC, Rayport S, Felsher DW, Dang CV. Targeted inhibition of tumor-specific glutaminase diminishes cell-autonomous tumorigenesis. J Clin Invest. 2015 Jun;125(6):2293-306. doi: 10.1172/JCI75836. Epub 2015 Apr 27. PMID: 25915584; PMCID: PMC4497742.
1: Sappington DR, Siegel ER, Hiatt G, Desai A, Penney RB, Jamshidi-Parsian A, Griffin RJ, Boysen G. Glutamine drives glutathione synthesis and contributes to radiation sensitivity of A549 and H460 lung cancer cell lines. Biochim Biophys Acta. 2016 Apr;1860(4):836-43. doi: 10.1016/j.bbagen.2016.01.021. Epub 2016 Jan 26. PubMed PMID: 26825773; PubMed Central PMCID: PMC4768472. 2: Lee SY, Jeon HM, Ju MK, Jeong EK, Kim CH, Park HG, Han SI, Kang HS. Dlx-2 and glutaminase upregulate epithelial-mesenchymal transition and glycolytic switch. Oncotarget. 2016 Jan 11. doi: 10.18632/oncotarget.6879. [Epub ahead of print] PubMed PMID: 26771232. 3: Chakrabarti G, Moore ZR, Luo X, Ilcheva M, Ali A, Padanad M, Zhou Y, Xie Y, Burma S, Scaglioni PP, Cantley LC, DeBerardinis RJ, Kimmelman AC, Lyssiotis CA, Boothman DA. Targeting glutamine metabolism sensitizes pancreatic cancer to PARP-driven metabolic catastrophe induced by ß-lapachone. Cancer Metab. 2015 Oct 12;3:12. doi: 10.1186/s40170-015-0137-1. eCollection 2015. PubMed PMID: 26462257; PubMed Central PMCID: PMC4601138. 4: Hernandez-Davies JE, Tran TQ, Reid MA, Rosales KR, Lowman XH, Pan M, Moriceau G, Yang Y, Wu J, Lo RS, Kong M. Vemurafenib resistance reprograms melanoma cells towards glutamine dependence. J Transl Med. 2015 Jul 3;13:210. doi: 10.1186/s12967-015-0581-2. PubMed PMID: 26139106; PubMed Central PMCID: PMC4490757. 5: Xiang Y, Stine ZE, Xia J, Lu Y, O'Connor RS, Altman BJ, Hsieh AL, Gouw AM, Thomas AG, Gao P, Sun L, Song L, Yan B, Slusher BS, Zhuo J, Ooi LL, Lee CG, Mancuso A, McCallion AS, Le A, Milone MC, Rayport S, Felsher DW, Dang CV. Targeted inhibition of tumor-specific glutaminase diminishes cell-autonomous tumorigenesis. J Clin Invest. 2015 Jun;125(6):2293-306. doi: 10.1172/JCI75836. Epub 2015 Apr 27. PubMed PMID: 25915584; PubMed Central PMCID: PMC4497742. 6: Polletta L, Vernucci E, Carnevale I, Arcangeli T, Rotili D, Palmerio S, Steegborn C, Nowak T, Schutkowski M, Pellegrini L, Sansone L, Villanova L, Runci A, Pucci B, Morgante E, Fini M, Mai A, Russo MA, Tafani M. SIRT5 regulation of ammonia-induced autophagy and mitophagy. Autophagy. 2015;11(2):253-70. doi: 10.1080/15548627.2015.1009778. PubMed PMID: 25700560; PubMed Central PMCID: PMC4502726. 7: McDonald CJ, Acheff E, Kennedy R, Taylor L, Curthoys NP. Effect of lysine to alanine mutations on the phosphate activation and BPTES inhibition of glutaminase. Neurochem Int. 2015 Sep;88:10-4. doi: 10.1016/j.neuint.2014.12.003. Epub 2014 Dec 12. PubMed PMID: 25510640; PubMed Central PMCID: PMC4465886. 8: Emadi A, Jun SA, Tsukamoto T, Fathi AT, Minden MD, Dang CV. Inhibition of glutaminase selectively suppresses the growth of primary acute myeloid leukemia cells with IDH mutations. Exp Hematol. 2014 Apr;42(4):247-51. doi: 10.1016/j.exphem.2013.12.001. Epub 2013 Dec 11. PubMed PMID: 24333121. 9: Thomas AG, O'Driscoll CM, Bressler J, Kaufmann W, Rojas CJ, Slusher BS. Small molecule glutaminase inhibitors block glutamate release from stimulated microglia. Biochem Biophys Res Commun. 2014 Jan 3;443(1):32-6. doi: 10.1016/j.bbrc.2013.11.043. Epub 2013 Nov 19. PubMed PMID: 24269238; PubMed Central PMCID: PMC3927782. 10: Zhdanov AV, Waters AH, Golubeva AV, Dmitriev RI, Papkovsky DB. Availability of the key metabolic substrates dictates the respiratory response of cancer cells to the mitochondrial uncoupling. Biochim Biophys Acta. 2014 Jan;1837(1):51-62. doi: 10.1016/j.bbabio.2013.07.008. Epub 2013 Jul 23. PubMed PMID: 23891695. 11: Thomas AG, Rojas C, Tanega C, Shen M, Simeonov A, Boxer MB, Auld DS, Ferraris DV, Tsukamoto T, Slusher BS. Kinetic characterization of ebselen, chelerythrine and apomorphine as glutaminase inhibitors. Biochem Biophys Res Commun. 2013 Aug 23;438(2):243-8. doi: 10.1016/j.bbrc.2013.06.110. Epub 2013 Jul 10. PubMed PMID: 23850693; PubMed Central PMCID: PMC4094369. 12: 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. PubMed PMID: 23151085; PubMed Central PMCID: PMC3539823. 13: Thangavelu K, Pan CQ, Karlberg T, Balaji G, Uttamchandani M, Suresh V, Schüler H, Low BC, Sivaraman J. Structural basis for the allosteric inhibitory mechanism of human kidney-type glutaminase (KGA) and its regulation by Raf-Mek-Erk signaling in cancer cell metabolism. Proc Natl Acad Sci U S A. 2012 May 15;109(20):7705-10. doi: 10.1073/pnas.1116573109. Epub 2012 Apr 26. PubMed PMID: 22538822; PubMed Central PMCID: PMC3356676. 14: 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. PubMed PMID: 22225880; PubMed Central PMCID: PMC3345194. 15: DeLaBarre B, Gross S, Fang C, Gao Y, Jha A, Jiang F, Song J J, Wei W, Hurov JB. Full-length human glutaminase in complex with an allosteric inhibitor. Biochemistry. 2011 Dec 20;50(50):10764-70. doi: 10.1021/bi201613d. Epub 2011 Nov 18. PubMed PMID: 22049910. 16: Hartwick EW, Curthoys NP. BPTES inhibition of hGA(124-551), a truncated form of human kidney-type glutaminase. J Enzyme Inhib Med Chem. 2012 Dec;27(6):861-7. doi: 10.3109/14756366.2011.622272. Epub 2011 Oct 15. PubMed PMID: 21999665. 17: 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. PubMed PMID: 21045145; PubMed Central PMCID: PMC3058858. 18: Robinson MM, McBryant SJ, Tsukamoto T, Rojas C, Ferraris DV, Hamilton SK, Hansen JC, Curthoys NP. Novel mechanism of inhibition of rat kidney-type glutaminase by bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide (BPTES). Biochem J. 2007 Sep 15;406(3):407-14. PubMed PMID: 17581113; PubMed Central PMCID: PMC2049044.