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

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

doi:10.1016/j.jgg.2020.06.001

Volume 47 Issue 7

Jul. 2020

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Article Navigation > Journal of Genetics and Genomics > 2020 > 47(7): 389-395

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

doi: 10.1016/j.jgg.2020.06.001

Yicheng Chen^{a, c},
Yiqing Zhao^{a, c},
David L. Bajor^{b, c, d},
Zhenghe Wang^{a, c},
J. Eva Selfridge^{b, c, d}

a
Department of Genetics and Genome Sciences, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH, 44106, USA
b
Department of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH, 44106, USA
c
Case Comprehensive Cancer Center, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH, 44106, USA
d
Seidman Cancer Center, University Hospitals Cleveland Medical Center, 11100 Euclid Avenue, Cleveland, OH, 44106, USA

More Information

Corresponding author: E-mail address: zxw22@case.edu (Zhenghe Wang); E-mail address: jennifer.selfridge@uhhospitals.org (J. Eva Selfridge)
Publish Date: 2020-07-25

Abstract

Abstract

Many cancer types reprogram their metabolism to become addicted to glutamine. One of the critical enzymes in the utilization of glutamine in these cells is glutaminase. CB-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 metabolism. Despite 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 trials. Thus, we developed an assay based on the cellular thermal shift assay technique using AlphaLISA technology to show that CB-839 specifically engages glutaminase in colon cancer cell lines in vitro and in minute quantities of mouse xenograft tumors. Notably, we show that this assay detects CB-839 binding to glutaminase in platelets of patients collected while receiving CB-839 on a clinical trial. This 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 in future studies designed to screen other inhibitors of glutaminase.
- Glutaminase,
- Method,
- Cancer

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References(15)

References

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