The synthesis and effects of a novel TRPC6 inhibitor, BP3112, on hepatocellular carcinoma
Aims: Transient receptor potential canonical-6 (TRPC6) is a therapeutic target for hepatocellular carcinoma. The authors aimed to synthesize and determine whether indole-2-carboxamide derivatives have anti-hepatocellular carcinoma activities targeting TRPC6. Materials & methods: Molecular docking was carried out to design these derivatives. The top five compounds were synthesized for activity validation using microscale thermophoresis. Cell cytotoxicity, flow cytometry, western blotting and cell transfection were used to investigate the anti-hepatocellular carcinoma activities and mechanisms in vitro. Xenografts of nude mice were used for in vivo evaluation. Results: The indole-2-carboxamide derivative, BP3112, promoted apoptosis and G1-phase arrest in HCCs via inhibiting TRPC6, and dose-dependently inhibit tumor growth in vivo. Conclusion: BP3112 as a specific inhibitor of TRPC6 is a potential therapeutic agent for hepatocellular carcinoma.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
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| Enthalten in: |
Future medicinal chemistry - 15(2023), 7 vom: 18. Apr., Seite 629-646 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Qiao, Ruizhi [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 10.05.2023 Date Revised 11.05.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.4155/fmc-2022-0313 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM356357104 |
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| 100 | 1 | |a Qiao, Ruizhi |e verfasserin |4 aut | |
| 245 | 1 | 4 | |a The synthesis and effects of a novel TRPC6 inhibitor, BP3112, on hepatocellular carcinoma |
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| 500 | |a Date Completed 10.05.2023 | ||
| 500 | |a Date Revised 11.05.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Aims: Transient receptor potential canonical-6 (TRPC6) is a therapeutic target for hepatocellular carcinoma. The authors aimed to synthesize and determine whether indole-2-carboxamide derivatives have anti-hepatocellular carcinoma activities targeting TRPC6. Materials & methods: Molecular docking was carried out to design these derivatives. The top five compounds were synthesized for activity validation using microscale thermophoresis. Cell cytotoxicity, flow cytometry, western blotting and cell transfection were used to investigate the anti-hepatocellular carcinoma activities and mechanisms in vitro. Xenografts of nude mice were used for in vivo evaluation. Results: The indole-2-carboxamide derivative, BP3112, promoted apoptosis and G1-phase arrest in HCCs via inhibiting TRPC6, and dose-dependently inhibit tumor growth in vivo. Conclusion: BP3112 as a specific inhibitor of TRPC6 is a potential therapeutic agent for hepatocellular carcinoma | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Ca2+ | |
| 650 | 4 | |a TRPC6 | |
| 650 | 4 | |a cell cycle | |
| 650 | 4 | |a computer-aided drug design | |
| 650 | 4 | |a hepatocellular carcinoma | |
| 650 | 4 | |a indole-2-carboxamide | |
| 650 | 7 | |a TRPC6 Cation Channel |2 NLM | |
| 650 | 7 | |a Indoles |2 NLM | |
| 650 | 7 | |a TRPC6 protein, human |2 NLM | |
| 650 | 7 | |a Trpc6 protein, mouse |2 NLM | |
| 700 | 1 | |a Fan, Xin |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Lei |e verfasserin |4 aut | |
| 700 | 1 | |a Dong, Dianchao |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Yang |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Detai |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Guangyuan |e verfasserin |4 aut | |
| 700 | 1 | |a Tang, Na |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yubo |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Xiao-Qiang |e verfasserin |4 aut | |
| 700 | 1 | |a Ren, Li |e verfasserin |4 aut | |
| 700 | 1 | |a Cao, Wei |e verfasserin |4 aut | |
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