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1mg |
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5mg |
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10mg |
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25mg |
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50mg |
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Purity: ≥98%
BPTES is a potent and selective allosteric Glutaminase GLS1 (KGA) inhibitor with IC50 of 0.16 μM. BPTES has an IC50 of 0.18 μM for inhibiting glutaminase activity expressed in human kidney cells and an IC50 of 80-120 nM for inhibiting glutamate efflux by microglia. In D54 cells with mutated IDH1, BPTES preferentially slows down cell proliferation. Moreover, BPTES raises glycolytic intermediates, decreases glutamate and α-KG levels, and inhibits glutaminase activity. The growth of mHCC 3.4 cells, which are derived from LAP/MYC tumors, is inhibited by BPTES (10 μM). By preventing DNA replication, BPTES also stunts the growth of MYC-dependent P493 cells, resulting in cell death and fragmentation.
Targets |
Glutaminase GLS1 (IC50 = 0.16 μM)
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ln Vitro |
BPTES has an IC50 of 0.18 μM for inhibiting glutaminase activity expressed in human kidney cells and an IC50 of 80-120 nM for inhibiting glutamate efflux by microglia.[1] In D54 cells harboring mutant IDH1, BPTES preferentially inhibits cell proliferation. Moreover, BPTES raises glycolytic intermediates, decreases glutamate and α-KG levels, and inhibits glutaminase activity.[2] The growth of mHCC 3.4 cells, which are derived from LAP/MYC tumors, is inhibited by BPTES (10 μM). By preventing DNA replication, BPTES also stunts the growth of MYC-dependent P493 cells, resulting in cell death and fragmentation.[3]
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ln Vivo |
BPTES (12.5 mg/kg, i.p.) prolongs survival in LAP/MYC mice without significantly affecting MYC, GLS, or GLS2 levels. In mice with P493 tumor xenografts, BPTES (200 μg/mouse, i.p.) also suppresses the growth of tumor cells.[3]
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Enzyme Assay |
Assay plates are made with two microliters of the test compound per well in DMSO. The enzyme is diluted in glutaminase assay buffer to 1 unit (liver) or 0.8 unit (kidney)/100 μL, and Multidrop adds 100 μL of the diluted enzyme to each well of the assay plate. On a TiterMix 100, the contents are combined by shaking vigorously for one minute. After preincubating the plates for 20 minutes at room temperature (RT) to facilitate the binding of test compounds to glutaminase, Multidrop adds 50 μL of glutamine solution (7 mM in assay buffer) to each well. After shaking the contents vigorously for 30 seconds on a TiterMix 100, the plates are incubated at room temperature for 60 minutes for the liver or 90 minutes for the kidney. In order to halt the reactions, Multidrop adds 20 μL of HCl (0.3 N) to each well, and then shakes the mixture for 30 seconds on the TiterMix 100. In order to quantify glutamate, which is created when glutaminase catalyzes the hydrolysis of glutamine, glutamate dehydrogenase (GDH) oxidizes the compound to 2-oxoglutarate while simultaneously producing nicotinamide adenine dinucleotide (NADH) in its reduced form. A blue-purple formazan is formed when nitro blue tetrazolium (NBT) in the assay solution is reduced by NADH, which is catalyzed by phenazine methosulphate (PMS). At 540 nm, formazan absorption is directly correlated with glutamate concentration up to 200 μM. To allow the GDH reaction to form color, 50 μL of NBT/GDH reagent is added to each well using Multidrop and shaken for 30 seconds on TiterMix 100. The plates are then incubated at room temperature for 20 minutes or longer. By measuring formazan concentration and using a SpectraMax 340 to read OD540 nm, glutamate concentration can be calculated.
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Cell Assay |
In a 96-well black transparent bottom plate, cells are plated at a density of 500 cells/well. After 24 hours, the medium is replaced with the proper one (DMEM containing 4 mM glutamine, 10% FBS, 4.5 g/L, 1.5 g/L, or 0.1 g/L glucose). Compounds or DMSO are added 48 hours after plating. Each well receives 200 µL of media and alamarBlue added to it. A Victor3 plate reader is used to measure fluorescence at 48 or 72 hours (EGCG).
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Animal Protocol |
For the test, four-week-old female Foxn1nuathymic nude mice are utilized. Living tumor banks are created by propagating freshly excised pancreatic tumor samples from patients at the time of surgery from mouse to mouse. After four weeks postimplantation, mice are given the following treatments: 12.5 mg/kg BPTES intraperitoneally, 200 mg/kg CB-839 twice daily by oral gavage, 54 mg/kg BPTES-NPs (1.2 mg BPTES in 100 µL nanoparticles per mouse) by intravenous injection, blank-NPs (100 µL per mouse) by intravenous injection, 25 mg/kg LY 188011 intraperitoneally, or a combination of BPTES-NPs and LY 188011). For a total of six injections spread over 16 days, BPTES-NPs are administered once every three days.
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References |
Molecular Formula |
C24H24N6O2S3
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Molecular Weight |
524.68
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Exact Mass |
524.11
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Elemental Analysis |
C, 54.94; H, 4.61; N, 16.02; O, 6.10; S, 18.33
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CAS # |
314045-39-1
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Appearance |
Solid powder
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SMILES |
C1=CC=C(C=C1)CC(=O)NC2=NN=C(S2)CCSCCC3=NN=C(S3)NC(=O)CC4=CC=CC=C4
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InChi Key |
MDJIPXYRSZHCFS-UHFFFAOYSA-N
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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)
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Chemical Name |
2-phenyl-N-[5-[2-[2-[5-[(2-phenylacetyl)amino]-1,3,4-thiadiazol-2-yl]ethylsulfanyl]ethyl]-1,3,4-thiadiazol-2-yl]acetamide
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Synonyms |
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HS Tariff Code |
2934.99.9001
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Solubility (In Vitro) |
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Solubility (In Vivo) |
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Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 1.9059 mL | 9.5296 mL | 19.0592 mL | |
5 mM | 0.3812 mL | 1.9059 mL | 3.8118 mL | |
10 mM | 0.1906 mL | 0.9530 mL | 1.9059 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
(A–D) Metabolic effects of metformin on patient-derived orthotopic pancreatic tumors.Proc Natl Acad Sci U S A.2016 Sep 6;113(36):E5328-36. th> |
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Effect of glutamate supplement on the proliferation ofKRAS-mutant human-derived pancreatic cancer cells (P198).Proc Natl Acad Sci U S A.2016 Sep 6;113(36):E5328-36. td> |
BPTES-NPs selectively target the cycling tumor cell subpopulation.Proc Natl Acad Sci U S A.2016 Sep 6;113(36):E5328-36. td> |