Identification and characterization of a novel mutant isocitrate dehydrogenase 1 inhibitor for glioma treatment
Copyright © 2021 Elsevier Inc. All rights reserved..
Isocitrate dehydrogenase 1 (IDH1) mutant R132H, promoting the oncometabolite D-2-hydroxyglutarate (D2HG), is a driver mutation and an emerging therapeutic target in glioma. This study identified a novel mutant IDH1 inhibitor, WM17, by virtual screening and enzymatic confirmation. It could bind to and increase mutant IDH1 protein's thermostability in both endogenous heterozygous cells and exogenous overexpressed cells. Consequently, WM17 reversed the accumulation of D2HG and histone hypermethylation in IDH1 mutated cells. Finally, we concluded that WM17 significantly inhibited cell migration in IDH1 mutated glioma cells, although it has no apparent effect on cell proliferation. Further studies are guaranteed toward the development of WM17 as a therapeutic agent for IDH1 mutated glioma.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:551 |
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| Enthalten in: |
Biochemical and biophysical research communications - 551(2021) vom: 30. Apr., Seite 38-45 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhang, Na [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 10.06.2021 Date Revised 10.06.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.bbrc.2021.02.112 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM322715644 |
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| 245 | 1 | 0 | |a Identification and characterization of a novel mutant isocitrate dehydrogenase 1 inhibitor for glioma treatment |
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| 520 | |a Copyright © 2021 Elsevier Inc. All rights reserved. | ||
| 520 | |a Isocitrate dehydrogenase 1 (IDH1) mutant R132H, promoting the oncometabolite D-2-hydroxyglutarate (D2HG), is a driver mutation and an emerging therapeutic target in glioma. This study identified a novel mutant IDH1 inhibitor, WM17, by virtual screening and enzymatic confirmation. It could bind to and increase mutant IDH1 protein's thermostability in both endogenous heterozygous cells and exogenous overexpressed cells. Consequently, WM17 reversed the accumulation of D2HG and histone hypermethylation in IDH1 mutated cells. Finally, we concluded that WM17 significantly inhibited cell migration in IDH1 mutated glioma cells, although it has no apparent effect on cell proliferation. Further studies are guaranteed toward the development of WM17 as a therapeutic agent for IDH1 mutated glioma | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a D-2-hydroxyglutarate | |
| 650 | 4 | |a Glioma | |
| 650 | 4 | |a Mutant IDH1 | |
| 650 | 4 | |a WM17 | |
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| 650 | 7 | |a Benzeneacetamides |2 NLM | |
| 650 | 7 | |a Cadherins |2 NLM | |
| 650 | 7 | |a Histones |2 NLM | |
| 650 | 7 | |a Imidazoles |2 NLM | |
| 650 | 7 | |a Mutant Proteins |2 NLM | |
| 650 | 7 | |a Isocitrate Dehydrogenase |2 NLM | |
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| 700 | 1 | |a Zheng, Bowen |e verfasserin |4 aut | |
| 700 | 1 | |a Yao, Xiaojun |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Xiaoming |e verfasserin |4 aut | |
| 700 | 1 | |a Du, Jingjing |e verfasserin |4 aut | |
| 700 | 1 | |a Shen, Yunfu |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Zhe |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Junhe |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Qianyu |e verfasserin |4 aut | |
| 700 | 1 | |a Lan, Wenjian |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Wanjun |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Wenzhe |e verfasserin |4 aut | |
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