A facile and sensitive method of quantifying glutaminase binding to its ninhibitor CB-839 in tissues

作     者：Yicheng Chen Yiqing Zhao David L.Bajor Zhenghe Wang J.Eva Selfridge Yicheng Chen;Yiqing Zhao;David L.Bajor;Zhenghe Wang;J.Eva Selfridge

作者机构：Department of Genetics and Genome SciencesCase Western Reserve University10900 Euclid AvenueClevelandOH44106USA Department of MedicineCase Western Reserve University10900 Euclid AvenueClevelandOH.44106USA Case Comprehensive Cancer CenterCase Western Reserve University10900 Euclid AvenueClevelandOH44106USA Seidman Cancer CenterUniversity Hospitals Cleveland Medical CenterWOO Euclid AvenueClevelandOH44106USA 

出 版 物：《Journal of Genetics and Genomics》 (遗传学报（英文版）)

年 卷 期：2020年第47卷第7期

页      面：389-395页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 100701[医学-药物化学] 10[医学] 

基　　金：the Case Comprehensive Cancer Center's K12 award(5K12CA076917-22) the Clinical and Translational Science Collaborative TL1 training grant(1TL1TRO02549-01) NIH grants RO1CA196643,UH2CA223670,P5OCA150964,and P30 CA043703 a Stand Up to Cancer Colorectal Cancer Dream Team Translational Research Grant(SU2C-AACR-DT22-17).Stand Up to Cancer is a program of the Entertainment Industry Foundation 

主　　题：Glutaminase Method Cancer 

摘      要：Many cancer types reprogram their metabolism to become addicted to *** of the critical enzymes in the utilization of glutamine in these cells is ***-839(telaglenastat)is a drug that targets glutaminase that is currently being evaluated in many clinical trials for efficacy in various cancer types that are known to be driven by glutamine *** its use,there are limited assays available for testing the pharmacodynamic on-target effects of CB-839 on the limited,small-volume patient samples that are obtained in early-phase clinical ***,we developed an assay based on the cellular thermal shift assay technique using AlphalLlSA technology to show that CB-839 specifically engages glutaminase in colon cancer cell lines in vitro and in minute quantities of mouse xenograft ***,we show that this assay detects CB-839 binding to glutaminase in platelets of patients collected while receiving CB-839 on a clinical *** assay may be used to study the pharmacodynamic profile of CB-839 in very small tissue samples obtained from patients on a clinical trial and may be useful infuture studies designed to screen other in hibitors of glutaminase.