https://orcid.org/0000-0001-9257-7891
Abstract
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.
Graphical abstract:
Supplementary data
To view the supplementary data that accompany this paper please visit the journal website at:www.tandfonline.com/doi/full/10.2217/epi-2016-0184
Author contributions
R Qiao performed in silico modeling studies; synthesized, purified and verified chemical compounds; and wrote the original draft. X Fan performed the cell and mouse experiments and statistical analysis and wrote the original draft. R Qiao and X Fan contributed equally to this work. L Zhou helped perform in silico modeling studies and the cell culture. D Dong and D Liu helped perform synthesis experiments. Y Liu, G Ma, N Tang and Y Wang helped perform the cell and mouse experiments. X-Q Li and Y Liu analyzed experimental data and helped perform statistical analysis. W Cao and L Ren designed the study and analyzed experimental data. All authors contributed to writing the manuscript and approved the final version of the manuscript.
Financial & competing interests disclosure
This work was supported by the National Natural Science Foundation of China (grant nos. 81940245 and 82004059), The Natural Science Basic Research Program of Shaanxi Province (2023-JC-JQ-61), Special Foundation for Talents of Northwest A and F University (grant no. 2452017335). Shaanxi Administration of Traditional Chinese Medicine (grant nos. 2019-GJ-JC012, 2021-04-ZZ-001, 2021-QYPT and 2021-SLRH-YQ-004) and The Science and Technology Project of Shaanxi Province in China (grant nos. 2019PT23 and 2022YWZX-PG-01). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.
Ethical conduct of research
All animal studies were approved by the Animal Care Committee of Northwest A&F University (2021-3-10-3).