Discovery of JMJD7 inhibitors with the aid of virtual screening and bioactivity evaluation
Copyright © 2021 Elsevier Ltd. All rights reserved..
Jumonji-C (JmjC) domain-containing 7 (JMJD7), which is a 2-oxoglutarate (2OG)-dependent oxygenase, has been demonstrated to play an important role in the occurrence and development of a number of diseases, particularly cancer. Discovery of JMJD7 inhibitors is thus of great importance. Herein consensus docking/scoring strategy and bioactivity evaluation were used to identify JMJD7 inhibitors from various chemical databases. Seven active compounds were retrieved. The most potent compound, Cpd-3, showed an IC50 value of 6.62 μM against JMJD7. Further biophysical assays confirmed that Cpd-3 could efficiently bind to JMJD7 in vitro. Flexible docking was used to predict the binding mode of Cpd-3 with JMJD7. In a cellular assay, Cpd-3 displayed good inhibitory activity against cancer cell lines expressing a high level of JMJD7. As far as we know, Cpd-3 is the first JMJD7 inhibitor reported so far. Overall, this study established a good starting point for drug discovery targeting JMJD7.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:45 |
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| Enthalten in: |
Bioorganic & medicinal chemistry letters - 45(2021) vom: 01. Aug., Seite 128139 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhang, Wenqing [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 05.01.2022 Date Revised 05.01.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.bmcl.2021.128139 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM325975973 |
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| 520 | |a Copyright © 2021 Elsevier Ltd. All rights reserved. | ||
| 520 | |a Jumonji-C (JmjC) domain-containing 7 (JMJD7), which is a 2-oxoglutarate (2OG)-dependent oxygenase, has been demonstrated to play an important role in the occurrence and development of a number of diseases, particularly cancer. Discovery of JMJD7 inhibitors is thus of great importance. Herein consensus docking/scoring strategy and bioactivity evaluation were used to identify JMJD7 inhibitors from various chemical databases. Seven active compounds were retrieved. The most potent compound, Cpd-3, showed an IC50 value of 6.62 μM against JMJD7. Further biophysical assays confirmed that Cpd-3 could efficiently bind to JMJD7 in vitro. Flexible docking was used to predict the binding mode of Cpd-3 with JMJD7. In a cellular assay, Cpd-3 displayed good inhibitory activity against cancer cell lines expressing a high level of JMJD7. As far as we know, Cpd-3 is the first JMJD7 inhibitor reported so far. Overall, this study established a good starting point for drug discovery targeting JMJD7 | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a Consensus docking | |
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| 700 | 1 | |a Li, Linli |e verfasserin |4 aut | |
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