The synthesis and effects of a novel TRPC6 inhibitor, BP3112, on hepatocellular carcinoma.
Ruizhi QiaoXin FanLei ZhouDianchao DongYang LiuDetai LiuGuang-Yuan MaNa TangYubo WangXiao-Qiang LiLi RenWei CaoPublished in: Future medicinal chemistry (2023)
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.
Keyphrases
- molecular docking
- vascular smooth muscle cells
- flow cytometry
- single cell
- cell therapy
- molecular dynamics simulations
- oxidative stress
- endoplasmic reticulum stress
- type diabetes
- south africa
- angiotensin ii
- cell death
- signaling pathway
- cell cycle
- high fat diet induced
- mesenchymal stem cells
- blood brain barrier
- cancer therapy
- cerebral ischemia
- pi k akt
- clinical evaluation
- skeletal muscle