000877590 001__ 877590
000877590 005__ 20210130005134.0
000877590 0247_ $$2doi$$a10.1038/s41420-020-0258-3
000877590 0247_ $$2Handle$$a2128/25101
000877590 0247_ $$2altmetric$$aaltmetric:80043886
000877590 0247_ $$2pmid$$apmid:32337072
000877590 0247_ $$2WOS$$aWOS:000526352700001
000877590 037__ $$aFZJ-2020-02312
000877590 082__ $$a610
000877590 1001_ $$0P:(DE-HGF)0$$aKoch, Katharina$$b0
000877590 245__ $$aA comparative pharmaco-metabolomic study of glutaminase inhibitors in glioma stem-like cells confirms biological effectiveness but reveals differences in target-specificity
000877590 260__ $$aLondon$$bNature Publishing Group816700$$c2020
000877590 3367_ $$2DRIVER$$aarticle
000877590 3367_ $$2DataCite$$aOutput Types/Journal article
000877590 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1592490604_21100
000877590 3367_ $$2BibTeX$$aARTICLE
000877590 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000877590 3367_ $$00$$2EndNote$$aJournal Article
000877590 520__ $$aCancer cells upregulate anabolic processes to maintain high rates of cellular turnover. Limiting the supply ofmacromolecular precursors by targeting enzymes involved in biosynthesis is a promising strategy in cancer therapy.Several tumors excessively metabolize glutamine to generate precursors for nonessential amino acids, nucleotides,and lipids, in a process called glutaminolysis. Here we show that pharmacological inhibition of glutaminase (GLS)eradicates glioblastoma stem-like cells (GSCs), a small cell subpopulation in glioblastoma (GBM) responsible for therapyresistance and tumor recurrence. Treatment with small molecule inhibitors compound 968 and CB839 effectivelydiminished cell growth and in vitro clonogenicity of GSC neurosphere cultures. However, our pharmaco-metabolicstudies revealed that only CB839 inhibited GLS enzymatic activity thereby limiting the influx of glutamine derivatesinto the TCA cycle. Nevertheless, the effects of both inhibitors were highly GLS specific, since treatment sensitivitymarkedly correlated with GLS protein expression. Strikingly, we found GLS overexpressed in in vitro GSC models ascompared with neural stem cells (NSC). Moreover, our study demonstrates the usefulness of in vitro pharmaco-metabolomics to score target specificity of compounds thereby refining drug development and risk assessment.
000877590 536__ $$0G:(DE-HGF)POF3-552$$a552 - Engineering Cell Function (POF3-552)$$cPOF3-552$$fPOF III$$x0
000877590 588__ $$aDataset connected to CrossRef
000877590 7001_ $$0P:(DE-Juel1)132001$$aHartmann, Rudolf$$b1$$ufzj
000877590 7001_ $$0P:(DE-HGF)0$$aTsiampali, Julia$$b2
000877590 7001_ $$0P:(DE-HGF)0$$aUhlmann, Constanze$$b3
000877590 7001_ $$0P:(DE-HGF)0$$aNickel, Ann-Christin$$b4
000877590 7001_ $$0P:(DE-HGF)0$$aHe, Xiaoling$$b5
000877590 7001_ $$0P:(DE-HGF)0$$aKamp, Marcel A.$$b6
000877590 7001_ $$0P:(DE-Juel1)165921$$aSabel, Michael$$b7
000877590 7001_ $$0P:(DE-HGF)0$$aBarker, Roger A.$$b8
000877590 7001_ $$0P:(DE-HGF)0$$aSteiger, Hans-Jakob$$b9
000877590 7001_ $$0P:(DE-HGF)0$$aHänggi, Daniel$$b10
000877590 7001_ $$0P:(DE-Juel1)132029$$aWillbold, Dieter$$b11
000877590 7001_ $$0P:(DE-HGF)0$$aMaciaczyk, Jaroslaw$$b12
000877590 7001_ $$0P:(DE-HGF)0$$aKahlert, Ulf D.$$b13$$eCorresponding author
000877590 773__ $$0PERI:(DE-600)2842546-7$$a10.1038/s41420-020-0258-3$$gVol. 6, no. 1, p. 20$$n1$$p20$$tCell death discovery$$v6$$x2058-7716$$y2020
000877590 8564_ $$uhttps://juser.fz-juelich.de/record/877590/files/A%20comparative%20pharmaco-metabolomic%20study%20ofglutaminase%20inhibitors%20in%20glioma%20stem-like%20cellsconfirms%20biological%20effectiveness%20but%20revealsdifferences%20in%20target-specificity.pdf$$yOpenAccess
000877590 8564_ $$uhttps://juser.fz-juelich.de/record/877590/files/A%20comparative%20pharmaco-metabolomic%20study%20ofglutaminase%20inhibitors%20in%20glioma%20stem-like%20cellsconfirms%20biological%20effectiveness%20but%20revealsdifferences%20in%20target-specificity.pdf?subformat=pdfa$$xpdfa$$yOpenAccess
000877590 909CO $$ooai:juser.fz-juelich.de:877590$$pdnbdelivery$$pdriver$$pVDB$$popen_access$$popenaire
000877590 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)132001$$aForschungszentrum Jülich$$b1$$kFZJ
000877590 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)132029$$aForschungszentrum Jülich$$b11$$kFZJ
000877590 9131_ $$0G:(DE-HGF)POF3-552$$1G:(DE-HGF)POF3-550$$2G:(DE-HGF)POF3-500$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$aDE-HGF$$bKey Technologies$$lBioSoft – Fundamentals for future Technologies in the fields of Soft Matter and Life Sciences$$vEngineering Cell Function$$x0
000877590 9141_ $$y2020
000877590 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2020-01-11
000877590 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2020-01-11
000877590 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences$$d2020-01-11
000877590 915__ $$0StatID:(DE-HGF)1190$$2StatID$$aDBCoverage$$bBiological Abstracts$$d2020-01-11
000877590 915__ $$0LIC:(DE-HGF)CCBY4$$2HGFVOC$$aCreative Commons Attribution CC BY 4.0
000877590 915__ $$0StatID:(DE-HGF)0501$$2StatID$$aDBCoverage$$bDOAJ Seal$$d2020-01-11
000877590 915__ $$0StatID:(DE-HGF)0500$$2StatID$$aDBCoverage$$bDOAJ$$d2020-01-11
000877590 915__ $$0StatID:(DE-HGF)0111$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2020-01-11
000877590 915__ $$0StatID:(DE-HGF)0700$$2StatID$$aFees$$d2020-01-11
000877590 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2020-01-11
000877590 915__ $$0StatID:(DE-HGF)0510$$2StatID$$aOpenAccess
000877590 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bDOAJ : Blind peer review$$d2020-01-11
000877590 915__ $$0StatID:(DE-HGF)0561$$2StatID$$aArticle Processing Charges$$f2020-01-11
000877590 915__ $$0StatID:(DE-HGF)0310$$2StatID$$aDBCoverage$$bNCBI Molecular Biology Database$$d2020-01-11
000877590 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews$$d2020-01-11
000877590 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2020-01-11
000877590 915__ $$0StatID:(DE-HGF)0320$$2StatID$$aDBCoverage$$bPubMed Central$$d2020-01-11
000877590 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2020-01-11
000877590 9201_ $$0I:(DE-Juel1)IBI-7-20200312$$kIBI-7$$lStrukturbiochemie$$x0
000877590 980__ $$ajournal
000877590 980__ $$aVDB
000877590 980__ $$aUNRESTRICTED
000877590 980__ $$aI:(DE-Juel1)IBI-7-20200312
000877590 9801_ $$aFullTexts