Repurposing sodium stibogluconate as an uracil DNA glycosylase inhibitor against prostate cancer using a time-resolved oligonucleotide-based drug screening platform
Copyright © 2024 Elsevier Inc. All rights reserved..
Repurposing drugs can significantly reduce the time and costs associated with drug discovery and development. However, many drug compounds possess intrinsic fluorescence, resulting in aberrations such as auto-fluorescence, scattering and quenching, in fluorescent high-throughput screening assays. To overcome these drawbacks, time-resolved technologies have received increasing attention. In this study, we have developed a rapid and efficient screening platform based on time-resolved emission spectroscopy in order to screen for inhibitors of the DNA repair enzyme, uracil-DNA glycosylase (UDG). From a database of 1456 FDA/EMA-approved drugs, sodium stibogluconate was discovered as a potent UDG inhibitor. This compound showed synergistic cytotoxicity against 5-fluorouracil-resistant cancer cells. This work provides a promising future for time-resolved technologies for high-throughput screening (HTS), allowing for the swift identification of bioactive compounds from previously overlooked scaffolds due to their inherent fluorescence properties.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:144 |
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| Enthalten in: |
Bioorganic chemistry - 144(2024) vom: 15. Feb., Seite 107176 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Nao, Sang-Cuo [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 19.02.2024 Date Revised 19.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.bioorg.2024.107176 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Copyright © 2024 Elsevier Inc. All rights reserved. | ||
| 520 | |a Repurposing drugs can significantly reduce the time and costs associated with drug discovery and development. However, many drug compounds possess intrinsic fluorescence, resulting in aberrations such as auto-fluorescence, scattering and quenching, in fluorescent high-throughput screening assays. To overcome these drawbacks, time-resolved technologies have received increasing attention. In this study, we have developed a rapid and efficient screening platform based on time-resolved emission spectroscopy in order to screen for inhibitors of the DNA repair enzyme, uracil-DNA glycosylase (UDG). From a database of 1456 FDA/EMA-approved drugs, sodium stibogluconate was discovered as a potent UDG inhibitor. This compound showed synergistic cytotoxicity against 5-fluorouracil-resistant cancer cells. This work provides a promising future for time-resolved technologies for high-throughput screening (HTS), allowing for the swift identification of bioactive compounds from previously overlooked scaffolds due to their inherent fluorescence properties | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Shiu-Hin Chan, Daniel |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Xueliang |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Guo-Dong |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Jia |e verfasserin |4 aut | |
| 700 | 1 | |a Wong, Chun-Yuen |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Wanhe |e verfasserin |4 aut | |
| 700 | 1 | |a Leung, Chung-Hang |e verfasserin |4 aut | |
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