New CDK8 inhibitors as potential anti-leukemic agents - Design, synthesis and biological evaluation
Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved..
Cyclin-dependent kinase 8 (CDK8) plays a vital role in regulating cell transcription either through its association with the mediator complex or by the phosphorylation of transcription factors. CDK8-mediated activation of oncogenes has proved to be important in a variety of cancer types including hematological malignancies. We have designed and synthesized a series of new synthetic steroids. The compounds were evaluated as CDK8 inhibitors in vitro. The three most potent compounds exhibit Kd-values towards CDK8 in the low nanomolar range (3.5-18 nM). Furthermore, the compounds displayed selectivity for CDK8 in a panel of 465 different kinases. The cell studies indicated a selectivity to kill AML-cancer cell lines compared to normal cell lines.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:28 |
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| Enthalten in: |
Bioorganic & medicinal chemistry - 28(2020), 10 vom: 15. Mai, Seite 115461 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Solum, Eirik [VerfasserIn] |
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| Links: |
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| Themen: |
Anti-leukemia |
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| Anmerkungen: |
Date Completed 01.06.2021 Date Revised 01.06.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.bmc.2020.115461 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM308309863 |
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| 520 | |a Cyclin-dependent kinase 8 (CDK8) plays a vital role in regulating cell transcription either through its association with the mediator complex or by the phosphorylation of transcription factors. CDK8-mediated activation of oncogenes has proved to be important in a variety of cancer types including hematological malignancies. We have designed and synthesized a series of new synthetic steroids. The compounds were evaluated as CDK8 inhibitors in vitro. The three most potent compounds exhibit Kd-values towards CDK8 in the low nanomolar range (3.5-18 nM). Furthermore, the compounds displayed selectivity for CDK8 in a panel of 465 different kinases. The cell studies indicated a selectivity to kill AML-cancer cell lines compared to normal cell lines | ||
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| 700 | 1 | |a Herfindal, Lars |e verfasserin |4 aut | |
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