314045-39-1

Basic information

• Product Name: bis-2-(5-PhenylacetMido-1,2,4-Thiadiazol-2-yl)Ethyl Sulfide
• Synonyms: bis-2-(5-PhenylacetMido-1,2,4-Thiadiazol-2-yl)Ethyl Sulfide;bis-2-(5-phenylaQtMido-1,2,4-Thiadiazol-2-yl)Ethylsulfide;Bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide;BPTES;Glutaminase Inhibitor II, BPTES
• CAS NO: 314045-39-1
• Molecular Formula: C₂₄H₂₄N₆O₂S₃
• Molecular Weight: 528.71312
• Mol File: 314045-39-1.mol
• Article Data: 3

Chemical Properties

• Appearance: white to beige/
• Density: 1.420±0.06 g/cm3(Predicted)
• Storage Temp.: 2-8°C
• Solubility: DMSO: soluble10mg/mL, clear
• PKA: 9.13±0.50(Predicted)
• Stability: Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 2 months.
• CAS DataBase Reference: bis-2-(5-PhenylacetMido-1,2,4-Thiadiazol-2-yl)Ethyl Sulfide(CAS DataBase Reference)
• NIST Chemistry Reference: bis-2-(5-PhenylacetMido-1,2,4-Thiadiazol-2-yl)Ethyl Sulfide(314045-39-1)
• EPA Substance Registry System: bis-2-(5-PhenylacetMido-1,2,4-Thiadiazol-2-yl)Ethyl Sulfide(314045-39-1)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26
• WGK Germany: 3
• Hazardous Substances Data: 314045-39-1(Hazardous Substances Data)

Usage

Description

Bis-2-(5-PhenylacetMido-1,2,4-Thiadiazol-2-yl)Ethyl Sulfide, also known as BPTES, is a potent and selective allosteric inhibitor of kidney-type glutaminase (GLS1). It is characterized by its ability to selectively inhibit GLS1 over GLS2, g-glutamyl transpeptidase, and glutamate dehydrogenase. BPTES plays a crucial role in shutting down an alternative energy-generating glutaminolysis pathway in P493 cells under conditions of glucose deprivation or hypoxia. Additionally, it has been shown to reduce the growth of P493 cell xenografts by 50% over a 10-day treatment period and increase PD-L1 expression in cancer cells. Furthermore, BPTES has demonstrated the ability to clear senescent cells and improve various age-related disorders in a geriatric mouse model.

Uses

Used in Pharmaceutical Industry:
BPTES is used as a glutaminase inhibitor for targeting cancer cells that rely on glutamine for growth and survival. By inhibiting GLS1, BPTES disrupts the glutaminolysis pathway, which is an alternative energy source for cancer cells, especially under conditions of glucose deprivation or hypoxia. This inhibition can lead to reduced tumor growth and potentially enhance the effectiveness of other cancer treatments.
Used in Cancer Research:
In cancer research, BPTES is utilized to study the role of glutamine metabolism in cancer cell growth and survival. Its ability to selectively inhibit GLS1 makes it a valuable tool for understanding the underlying mechanisms of cancer cell metabolism and for identifying potential therapeutic targets.
Used in Aging and Age-Related Disorders Research:
BPTES is used in research focused on aging and age-related disorders due to its demonstrated ability to clear senescent cells and improve various age-related conditions in a geriatric mouse model. This suggests that BPTES may have potential applications in the development of therapies aimed at addressing the effects of aging and improving overall health in older individuals.
Used in Drug Delivery Systems:
Similar to gallotannin, BPTES could potentially be incorporated into novel drug delivery systems to enhance its applications and efficacy against cancer cells. Various organic and metallic nanoparticles could be employed as carriers for BPTES delivery, aiming to improve its delivery, bioavailability, and therapeutic outcomes.

Biochem/physiol Actions

Vaccinia virus (VACV) requires glutamine metabolism for its optimal replication. Inhibition of glutaminolysis by bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide (BPTES) can be a potential method to treat poxvirus infections.

References

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

Upstream product

• 303065-25-0 5,5'-(thiobis(ethane-2,1-diyl))bis(1,3,4-thiadiazol-2-amine) 
• 103-80-0 phenylacetyl chloride 
• 111-17-1 4-thiaheptane-1,7-dioic acid 
• 103-82-2 phenylacetic acid 

Downstream Products

• 1439389-42-0 C₃₄H₄₀N₆O₆S₃ 
• 1439389-41-9 C₂₉H₃₂N₆O₄S₃ 
• 1610603-85-4 5,5'-(thiobis(ethane-2,1-diyl))bis(N-phenethyl-1,3,4-thiadiazol-2-amine) 

Relevant articles and documents

Novel 1,3,4-Selenadiazole-Containing Kidney-Type Glutaminase Inhibitors Showed Improved Cellular Uptake and Antitumor Activity

Kidney-type glutaminase [KGA/isoenzyme glutaminase C (GAC)] is becoming an important tumor metabolism target in cancer chemotherapy. Its allosteric inhibitor, CB839, showed early promise in cancer therapeutics but limited efficacy in in vivo cancer models. To improve the in vivo activity, we explored a bioisostere replacement of the sulfur atom in bis-2-(5-phenylacetamido-1,2,4-thiadiazol)ethyl sulfide and CB839 analogues with selenium using a novel synthesis of the selenadiazole moiety from carboxylic acids or nitriles. The resulting selenadiazole compounds showed enhanced KGA inhibition, more potent induction of reactive oxygen species, improved inhibition of cancer cells, and higher cellular and tumor accumulation than the corresponding sulfur-containing molecules. However, both CB839 and its selenium analogues show incomplete inhibition of the tested cancer cells, and a partial reduction in tumor size was observed in both the glutamine-dependent HCT116 and aggressive H22 liver cancer xenograft models. Despite this, tumor tissue damage and prolonged survival were observed in animals treated with the selenium analogue of CB839.

Design, synthesis, and pharmacological evaluation of bis-2-(5- phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide 3 (BPTES) analogs as glutaminase inhibitors

Bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide (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. In an attempt to identify more potent GLS inhibitors with improved drug-like molecular properties, a series of BPTES analogs were synthesized and evaluated. Our structure-activity relationship (SAR) studies revealed that some truncated analogs retained the potency of BPTES, presenting an opportunity to improve its aqueous solubility. One of the analogs, N-(5-{2-[2-(5-amino-[1,3,4] thiadiazol-2-yl)-ethylsulfanyl]-ethyl}-[1,3,4]thiadiazol-2-yl) -2-phenyl-acetamide 6, exhibited similar potency and better solubility relative to BPTES and attenuated the growth of P493 human lymphoma B cells in vitro as well as in a mouse xenograft model.