BPTES
BPTES is a potent and selective kidney-type glutaminase (GLS) inhibitor [1], with a Ki value of approx. 3 μM [2].
Glutaminase hydrolyzes glutamine into ammonia and glutamate. In mammalian tissues, two glutaminase isoforms derived from structurally related but distinct genes, are expressed. GLS is widely distributed in extra-hepatic tissues. Liver-type glutaminase (GLS2) is primarily found in adult liver. GLS is critical in glutaminolysis for many proliferating cells, especially malignant cells with rapid growth [1].
Cell lines with mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) were used. In all IDH1-mutant AML cells, compared with DMSO, exposure to 20 µmol/L BPTES reduced the cell growth by approximately 50% on day 4. 20 µmol/L BPTES was not significantly different from 40 µmol/L BPTES in the reduction effect. Treatment without drug was not significantly different from treatment with DMSO in the growth of cells. BPTES did not significantly affect the cell growth of wild type AML cells [3]. In tumor cells, BPTES inhibited the conversion of glutamine into glutamate [4].
Glutamate is a substrate of GPT in the transamination of pyruvate to alanine. Compared with controls, BPTES treatment reduced the pyruvate-to-alanine conversion in animals. In replicated experiments, BPTES significantly reduce the alanine-to-pyruvate (Ala/Pyr) flux ratio [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. Journal of medicinal chemistry, 2012, 55(23): 10551-10563.
[2]. Robinson MM, Mcbryant SJ, Tsukamoto T, et al. Novel mechanism of inhibition of rat kidney-type glutaminase by bis-2-(5-phenylacetamido-1, 2, 4-thiadiazol-2-yl) ethyl sulfide (BPTES). Biochemical Journal, 2007, 406(3): 407-414.
[3]. Emadi A, Jun SA, Tsukamoto T, et al. Inhibition of glutaminase selectively suppresses the growth of primary acute myeloid leukemia cells with IDH mutations. Experimental hematology, 2014, 42(4): 247-251.
[4]. Dutta P, Le A, Vander Jagt DL, et al. Evaluation of LDH-A and glutaminase inhibition in vivo by hyperpolarized 13C-pyruvate magnetic resonance spectroscopy of tumors. Cancer research, 2013, 73(14): 4190-4195.
- 1. Jiang-Sha Zhao, Shuo Shi, et al. "Glutamine synthetase licenses APC/C-mediated mitotic progression to drive cell growth." Nat Metab. 2022 Feb;4(2):239-253. PMID: 35145325
- 2. Wu WC, Sun HW, et al. "Immunosuppressive immature myeloid cell generation is controlled by glutamine metabolism in human cancer." Cancer Immunol Res. 2019 Aug 6. pii: canimm.0902.2018. PMID:31387898
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 524.68 |
| Cas No. | 314045-39-1 |
| Formula | C24H24N6O2S3 |
| Solubility | insoluble in H2O; insoluble in EtOH; ≥18 mg/mL in DMSO |
| Chemical Name | (1Z,1'Z)-N',N''-(5,5'-(thiobis(ethane-2,1-diyl))bis(1,3,4-thiadiazole-5,2-diyl))bis(2-phenylacetimidic acid) |
| SDF | Download SDF |
| Canonical SMILES | O/C(CC1=CC=CC=C1)=N\C2=NN=C(S2)CCSCCC(S3)=NN=C3/N=C(O)/CC4=CC=CC=C4 |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment [1]: | |
|
Cell lines |
AML cells |
|
Preparation method |
The solubility of this compound in DMSO is > 18 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months. |
|
Reacting condition |
20 or 40 μM |
|
Applications |
After being exposed to 20 μM BPTES for 4 days, all IDH1-mutant AML cells were reduced approximately by 50%. The doses of 20 μM and 40 μM exhibited similar effects. However, BPTES did not significantly affect the growth of wild type AML cells. According to the mass spectrometry analysis, BPTES did not significantly change α-KG or 2-HG levels in IDH-mutant or wild type AML cells. |
| Animal experiment [2]: | |
|
Animal models |
Mice harboring P493 tumor xenografts |
|
Dosage form |
200 μg; i.p.; every 3 days for 10 days |
|
Applications |
In mice harboring P493 tumor xenografts, BPTES reduced tumor growth by approximately 50% over a 10-day treatment period. However, BPTES did not inhibit the growth of P493 xenografts expressing wild type GLS or BPTES-resistant mutant GLS K325A. According to the metabolic analysis of P493 xenografts, BPTES treatment increased tumor glutamine levels and decreased glutamate levels. |
|
Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
|
References: [1]. Emadi A, Jun SA, Tsukamoto T, et al. Inhibition of glutaminase selectively suppresses the growth of primary acute myeloid leukemia cells with IDH mutations. Experimental hematology, 2014, 42(4): 247-251. [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. |
|
Quality Control & MSDS
- View current batch:
Chemical structure
Related Biological Data
