Discovery of Potential Neuroprotective Agents against Paclitaxel-Induced Peripheral Neuropathy
Chemotherapy-induced neurotoxicity is a common adverse effect of cancer treatment. No medication has been shown to be effective in the prevention or treatment of chemotherapy-induced neurotoxicity. Using minoxidil as an initial template for structural modifications in conjunction with an in vitro neurite outgrowth assay, an image-based high-content screening platform, and mouse behavior models, an effective neuroprotective agent CN016 was discovered. Our results showed that CN016 could inhibit paclitaxel-induced inflammatory responses and infiltration of immune cells into sensory neurons significantly. Thus, the suppression of proinflammatory factors elucidates, in part, the mechanism of action of CN016 on alleviating paclitaxel-induced peripheral neuropathy. Based on excellent efficacy in improving behavioral functions, high safety profiles (MTD > 500 mg/kg), and a large therapeutic window (MTD/MED > 50) in mice, CN016 might have great potential to become a peripherally neuroprotective agent to prevent neurotoxicity caused by chemotherapeutics as typified by paclitaxel.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:65 |
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| Enthalten in: |
Journal of medicinal chemistry - 65(2022), 6 vom: 24. März, Seite 4767-4782 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Chen, Yi-Fan [VerfasserIn] |
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| Links: |
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| Themen: |
Antineoplastic Agents |
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| Anmerkungen: |
Date Completed 06.05.2022 Date Revised 06.05.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1021/acs.jmedchem.1c01912 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM337657424 |
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| 520 | |a Chemotherapy-induced neurotoxicity is a common adverse effect of cancer treatment. No medication has been shown to be effective in the prevention or treatment of chemotherapy-induced neurotoxicity. Using minoxidil as an initial template for structural modifications in conjunction with an in vitro neurite outgrowth assay, an image-based high-content screening platform, and mouse behavior models, an effective neuroprotective agent CN016 was discovered. Our results showed that CN016 could inhibit paclitaxel-induced inflammatory responses and infiltration of immune cells into sensory neurons significantly. Thus, the suppression of proinflammatory factors elucidates, in part, the mechanism of action of CN016 on alleviating paclitaxel-induced peripheral neuropathy. Based on excellent efficacy in improving behavioral functions, high safety profiles (MTD > 500 mg/kg), and a large therapeutic window (MTD/MED > 50) in mice, CN016 might have great potential to become a peripherally neuroprotective agent to prevent neurotoxicity caused by chemotherapeutics as typified by paclitaxel | ||
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| 700 | 1 | |a Lee, Hao-Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Jinq-Chyi |e verfasserin |4 aut | |
| 700 | 1 | |a Yeh, Teng-Kuang |e verfasserin |4 aut | |
| 700 | 1 | |a Chang, Jang-Yang |e verfasserin |4 aut | |
| 700 | 1 | |a Chou, Ming-Chen |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Hui-Ling |e verfasserin |4 aut | |
| 700 | 1 | |a Lai, Yen-Po |e verfasserin |4 aut | |
| 700 | 1 | |a Song, Jen-Shin |e verfasserin |4 aut | |
| 700 | 1 | |a Yeh, Kai-Chia |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Chiung-Tong |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Chia-Jui |e verfasserin |4 aut | |
| 700 | 1 | |a Shia, Kak-Shan |e verfasserin |4 aut | |
| 700 | 1 | |a Shen, Meng-Ru |e verfasserin |4 aut | |
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