1415397-86-2

Upstream product

• 626-86-8 adipinic acid monoethyl ester 
• 118863-95-9 5-(5-amino-1,3,4-thiadiazol-2-yl)pentanoic acid 
• 103-80-0 phenylacetyl chloride 

Downstream Products

• 1415397-18-0 N-(5-(4-(5-amino-1,3,4-thiadiazol-2-yl)butyl)-1,3,4-thiadiazol-2-yl)-2-phenylacetamide 
• 1415397-35-1 C₂₁H₂₉N₅O₂S 
• 1415397-36-2 C₂₂H₃₁N₅O₂S 
• 1415397-38-4 C₂₂H₃₁N₅O₂S 
• 1415397-40-8 C₂₂H₃₁N₅O₂S 
• 1415397-43-1 C₂₂H₃₁N₅O₃S 
• 1415397-49-7 C₁₇H₂₃N₅O₂S 
• 1415397-45-3 C₂₈H₃₅N₅O₂S 
• 1415397-53-3 C₂₁H₃₁N₅O₂S 
• 1415397-56-6 C₁₉H₂₆N₄O₂S 
• 1415397-59-9 C₂₀H₂₈N₄O₂S 
• 1415397-62-4 C₂₂H₂₄N₄O₂S 
• 1415397-66-8 C₂₄H₂₉N₅O₂S 
• 1415397-70-4 C₂₃H₂₃F₃N₄O₂S 

Relevant academic research and scientific papers

Glutamine GLS1 inhibitor containing triazolium structure or pharmaceutically acceptable salt thereof and preparation method and application of glutamine GLS1 inhibitor or pharmaceutically acceptable salt thereof

The invention discloses a glutaminase GLS1 inhibitor containing a triazolium structure or pharmaceutically acceptable salt thereof and a preparation method and application of the glutamine GLS1 inhibitor or the pharmaceutically acceptable salt thereof. A series of compounds containing the triazolium structure have glutaminase inhibitory activity and can be used for treating diseases and symptoms associated with glutaminase dysfunction or increased glutaminase activity. The compounds can effectively bind to the allosteric site of glutaminase, the conformation of glutaminase can be changed, andthe biological function development is blocked. In-vitro experiments show that the compounds have good inhibitory activity on various glutamine-dependent cancer cells such as colon cancer, triple negative breast cancer and lung cancer.

Development and Characterization of a Fluorescent Probe for GLS1 and the Application for High-Throughput Screening of Allosteric Inhibitors

Glutaminase (GLS1) is a cancer energy metabolism protein which plays a predominant role in cell growth and proliferation. Because of its major involvement in malignant tumor, small-molecule GLS1 inhibitors are urgently needed to assess its therapeutic potential and for probing their underlying biology function. Recent studies showed that targeting the allosteric binding site represented a promising strategy for identifying potent and selective GLS1 inhibitors. Herein, we present the synthesis of two fluorescent probes targeting the allosteric binding site of GLS1 and their usage as mechanistic tools in multiple applicable assay platform. The fluorescence polarization (FP)-based binding assay enables easy, fast, and reliable screen of allosteric inhibitors from our in-house compound library obtained through click chemistry method. The obtained compound C147 (named as CPU-L1) has been proved to be more potent and with greater solubility than the control compound CB839, which could serve as promising leads for further optimization as novel GLS1 inhibitors.

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.