Identification of a small molecule inhibitor of 3-phosphoglycerate dehydrogenase to target serine biosynthesis in cancers DOI Creative Commons

Edouard Mullarky,

Natasha C. Lucki,

Reza Beheshti Zavareh

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2016, Volume and Issue: 113(7), P. 1778 - 1783

Published: Feb. 1, 2016

Cancer cells reprogram their metabolism to promote growth and proliferation. The genetic evidence pointing the importance of amino acid serine in tumorigenesis is striking. gene encoding enzyme 3-phosphoglycerate dehydrogenase (PHGDH), which catalyzes first committed step biosynthesis, overexpressed tumors cancer cell lines via focal amplification nuclear factor erythroid-2-related 2 (NRF2)-mediated up-regulation. PHGDH-overexpressing are exquisitely sensitive ablation pathway. Here, we report discovery a selective small molecule inhibitor PHGDH, CBR-5884, identified by screening library 800,000 drug-like compounds. CBR-5884 inhibited de novo synthesis was selectively toxic with high biosynthetic activity. Biochemical characterization revealed that it noncompetitive showed time-dependent onset inhibition disrupted oligomerization state PHGDH. identification PHGDH not only enables thorough preclinical evaluation as target cancers, but also provides tool study metabolism.

Language: Английский

Fundamentals of cancer metabolism DOI Creative Commons
Ralph J. DeBerardinis, Navdeep S. Chandel

Science Advances, Journal Year: 2016, Volume and Issue: 2(5)

Published: May 6, 2016

Researchers provide a conceptual framework to understand current knowledge of the fundamentals cancer metabolism.

Language: Английский

Citations

2518
Metabolomics: beyond biomarkers and towards mechanisms DOI
Caroline H. Johnson, Julijana Ivanišević, Gary Siuzdak

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2016, Volume and Issue: 17(7), P. 451 - 459

Published: March 16, 2016

Language: Английский

Citations

2192
Glucose feeds the TCA cycle via circulating lactate DOI
Sheng Hui, Jonathan M. Ghergurovich, Raphael J. Morscher

et al.

Nature, Journal Year: 2017, Volume and Issue: 551(7678), P. 115 - 118

Published: Oct. 18, 2017

Language: Английский

Citations

1402
Lactate Metabolism in Human Lung Tumors DOI Creative Commons
Brandon Faubert,

Kevin Y. Li,

Ling Cai

et al.

Cell, Journal Year: 2017, Volume and Issue: 171(2), P. 358 - 371.e9

Published: Oct. 1, 2017

Language: Английский

Citations

1103
Metabolic Heterogeneity in Human Lung Tumors DOI Creative Commons
Christopher T. Hensley, Brandon Faubert, Qing Yuan

et al.

Cell, Journal Year: 2016, Volume and Issue: 164(4), P. 681 - 694

Published: Feb. 1, 2016

Language: Английский

Citations

969
NMR Spectroscopy for Metabolomics Research DOI Creative Commons
Abdul‐Hamid Emwas, Raja Roy, Ryan T. McKay

et al.

Metabolites, Journal Year: 2019, Volume and Issue: 9(7), P. 123 - 123

Published: June 27, 2019

Over the past two decades, nuclear magnetic resonance (NMR) has emerged as one of three principal analytical techniques used in metabolomics (the other being gas chromatography coupled to mass spectrometry (GC-MS) and liquid with single-stage (LC-MS)). The relative ease sample preparation, ability quantify metabolite levels, high level experimental reproducibility, inherently nondestructive nature NMR spectroscopy have made it preferred platform for long-term or large-scale clinical metabolomic studies. These advantages, however, are often outweighed by fact that most techniques, including both LC-MS GC-MS, more sensitive than NMR, lower limits detection typically 10 100 times better. This review is intended introduce readers field NMR-based highlight advantages disadvantages It will also explore some unique strengths metabolomics, particularly regard isotope selection/detection, mixture deconvolution via 2D spectroscopy, automation, noninvasively analyze native tissue specimens. Finally, this a number emerging technologies strengthen its utility overcome inherent limitations applications.

Language: Английский

Citations

882
Identification of bioactive metabolites using activity metabolomics DOI
Markus M. Rinschen, Julijana Ivanišević, Martin Giera

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2019, Volume and Issue: 20(6), P. 353 - 367

Published: Feb. 27, 2019

Language: Английский

Citations

827
Glutaminolysis: A Hallmark of Cancer Metabolism DOI Open Access
Lifeng Yang, Sriram Venneti, Deepak Nagrath

et al.

Annual Review of Biomedical Engineering, Journal Year: 2017, Volume and Issue: 19(1), P. 163 - 194

Published: March 16, 2017

Glutamine is the most abundant circulating amino acid in blood and muscle critical for many fundamental cell functions cancer cells, including synthesis of metabolites that maintain mitochondrial metabolism; generation antioxidants to remove reactive oxygen species; nonessential acids (NEAAs), purines, pyrimidines, fatty cellular replication; activation signaling. In light pleiotropic role glutamine a comprehensive understanding metabolism essential development metabolic therapeutic strategies targeting cells. this article, we review oncogene-, tumor suppressor-, microenvironment-mediated regulation We describe mechanism glutamine's proliferation, metastasis, global methylation. Furthermore, highlight potential emphasize clinical application vivo assessment identifying new ways treat patients through glutamine-based therapy.

Language: Английский

Citations

704
The metabolism of cancer cells during metastasis DOI
Gabriele Bergers, Sarah‐Maria Fendt

Nature reviews. Cancer, Journal Year: 2021, Volume and Issue: 21(3), P. 162 - 180

Published: Jan. 18, 2021

Language: Английский

Citations

678
Deuterium‐ and Tritium‐Labelled Compounds: Applications in the Life Sciences DOI

Jens Atzrodt,

Volker Derdau, William J. Kerr

et al.

Angewandte Chemie International Edition, Journal Year: 2017, Volume and Issue: 57(7), P. 1758 - 1784

Published: Aug. 17, 2017

Hydrogen isotopes are unique tools for identifying and understanding biological chemical processes. isotope labelling allows the traceless direct incorporation of an additional mass or radioactive tag into organic molecule with almost no changes in its structure, physical properties, activity. Using deuterium-labelled isotopologues to study mass-spectrometric patterns generated from mixtures biologically relevant molecules drastically simplifies analysis. Such methods now providing unprecedented levels insight a wide continuously growing range applications life sciences beyond. Tritium (3 H), particular, has seen increase utilization, especially pharmaceutical drug discovery. The efforts costs associated synthesis labelled compounds more than compensated by enhanced molecular sensitivity during analysis high reliability data obtained. In this Review, advances application hydrogen described.

Language: Английский

Citations

644