Design, synthesis, and biological evaluation of novel bifunctional thyrointegrin antagonists for neuroblastoma
Copyright © 2021. Published by Elsevier Ltd..
Receptor-mediated cancer therapy has received much attention in the last few decades. Neuroblastoma and other cancers of the sympathetic nervous system highly express norepinephrine transporter (NET) and cell plasma membrane integrin αvβ3. Dual targeting of the NET and integrin αvβ3 receptors using a Drug-Drug Conjugate (DDC) might provide effective treatment strategy in the fight against neuroblastoma and other neuroendocrine tumors. In this work, we synthesized three dual-targeting BG-P400-TAT derivatives, dI-BG-P400-TAT, dM-BG-P400-TAT, and BG-P400-PAT containing di-iodobenzene, di-methoxybenzene, and piperazine groups, respectively. These derivatives utilize to norepinephrine transporter (NET) and the integrin αvβ3 receptor to simultaneously modulate both targets based on evaluation in a neuroblastoma animal model using the neuroblastoma SK-N-F1 cell line. Among the three synthesized agents, the piperazine substituted BG-P400-PAT exhibited potent integrin αvβ3 antagonism and reduced neuroblastoma tumor growth and cancer cell viability by >90%. In conclusion, BG-P400-PAT and derivatives represent a potential therapeutic approach in the management of neuroblastoma.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:42 |
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| Enthalten in: |
Bioorganic & medicinal chemistry - 42(2021) vom: 15. Juli, Seite 116250 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Karakus, Ozlem Ozen [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 15.12.2021 Date Revised 15.12.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.bmc.2021.116250 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM326666923 |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2021. Published by Elsevier Ltd. | ||
| 520 | |a Receptor-mediated cancer therapy has received much attention in the last few decades. Neuroblastoma and other cancers of the sympathetic nervous system highly express norepinephrine transporter (NET) and cell plasma membrane integrin αvβ3. Dual targeting of the NET and integrin αvβ3 receptors using a Drug-Drug Conjugate (DDC) might provide effective treatment strategy in the fight against neuroblastoma and other neuroendocrine tumors. In this work, we synthesized three dual-targeting BG-P400-TAT derivatives, dI-BG-P400-TAT, dM-BG-P400-TAT, and BG-P400-PAT containing di-iodobenzene, di-methoxybenzene, and piperazine groups, respectively. These derivatives utilize to norepinephrine transporter (NET) and the integrin αvβ3 receptor to simultaneously modulate both targets based on evaluation in a neuroblastoma animal model using the neuroblastoma SK-N-F1 cell line. Among the three synthesized agents, the piperazine substituted BG-P400-PAT exhibited potent integrin αvβ3 antagonism and reduced neuroblastoma tumor growth and cancer cell viability by >90%. In conclusion, BG-P400-PAT and derivatives represent a potential therapeutic approach in the management of neuroblastoma | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a Integrin αvβ3 | |
| 650 | 4 | |a Neuroblastoma | |
| 650 | 4 | |a Norepinephrine transporter (NET) | |
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| 700 | 1 | |a Mousa, Shaker A |e verfasserin |4 aut | |
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