| |  Online-Ressource |
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| Verfasst von: | Chaturvedi, Anuhar [VerfasserIn]  |
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| | Pusch, Stefan [VerfasserIn] |
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| | Stichel, Damian [VerfasserIn] |
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| | Bochtler, Tilmann [VerfasserIn] |
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| | Ho, Anthony Dick [VerfasserIn] |
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| | Deimling, Andreas von [VerfasserIn] |
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| | Rippe, Karsten [VerfasserIn] |
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| | Krämer, Alwin [VerfasserIn] |
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| Titel: | Pan-mutant-IDH1 inhibitor BAY1436032 is highly effective against human IDH1 mutant acute myeloid leukemia in vivo |
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| Verf.angabe: | A. Chaturvedi, L. Herbst, S. Pusch, L. Klett, R. Goparaju, D. Stichel, S. Kaulfuss, O. Panknin, K. Zimmermann, L. Toschi, R. Neuhaus, A. Haegebarth, H. Rehwinkel, H. Hess-Stumpp, M. Bauser, T. Bochtler, E.A. Struys, A. Sharma, A. Bakkali, R. Geffers, M.M. Araujo-Cruz, F. Thol, R. Gabdoulline, A. Ganser, A.D. Ho, A. von Deimling, K. Rippe, M. Heuser and A. Krämer |
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| E-Jahr: | 2017 |
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| Jahr: | 24 February 2017 |
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| Umfang: | 9 S. |
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| Fussnoten: | Gesehen am 15.11.2017 |
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| Titel Quelle: | Enthalten in: Leukemia |
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| Ort Quelle: | London : Springer Nature, 1997 |
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| Jahr Quelle: | 2017 |
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| Band/Heft Quelle: | 31(2017), 10, Seite 2020-2028 |
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| ISSN Quelle: | 1476-5551 |
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| Abstract: | Neomorphic mutations in isocitrate dehydrogenase 1 (IDH1) are frequently found in several human cancer types including acute myeloid leukemia (AML) and lead to the production of high levels of the oncometabolite (R)-2-hydroxyglutarate (R-2HG). Here we report the characterization of BAY1436032, a novel pan-mutant IDH1 inhibitor, both in vitro and in vivo. BAY1436032 specifically inhibits R-2HG production and colony growth, and induces myeloid differentiation of AML cells carrying IDH1R132H, IDH1R132C, IDH1R132G, IDH1R132L and IDH1R132S mutations. In addition, the compound impacts on DNA methylation and attenuates histone hypermethylation. Oral administration of BAY1436032 led to leukemic blast clearance, myeloid differentiation, depletion of leukemic stem cells and prolonged survival in two independent patient-derived xenograft IDH1 mutant AML mouse models. Together, BAY1436032 is highly effective against all major types of IDH1 mutant AML. |
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| DOI: | doi:10.1038/leu.2017.46 |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext: http://dx.doi.org/10.1038/leu.2017.46 |
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| | Volltext: https://www.nature.com/leu/journal/vaop/ncurrent/full/leu201746a.html |
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| | DOI: https://doi.org/10.1038/leu.2017.46 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| K10plus-PPN: | 1559164654 |
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| Verknüpfungen: | → Zeitschrift |
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Pan-mutant-IDH1 inhibitor BAY1436032 is highly effective against human IDH1 mutant acute myeloid leukemia in vivo / Chaturvedi, Anuhar [VerfasserIn]; 24 February 2017 (Online-Ressource)
