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Fibroblast growth factor receptor 4 (FGFR4) has been identified as a potential target due to its transmission of the FGF19 signaling pathway, which is critical to hepatocellular carcinoma (HCC). Therefore, focusing on the specific Cys552 of FGFR4 subtype, we designed and synthesized a novel family of 1,6-naphthyridin-2(1 H )-one derivatives as potent and highly selective FGFR4 inhibitors. Through detailed structural optimizations, the representative compound A34 exhibited improved FGFR4 inhibitory capability and selectivity and excellent anti-proliferative activities against FGFR4-dependent HCC cell lines. Additionally, A34 demonstrated remarkable antitumor efficacy in a Hep-3B HCC xenograft model, with favorable pharmacokinetic properties, and low risk of hERG toxicity. A34 also showed moderate inhibitory activities against the FGFR4 V550L mutant in vitro, which indicates that it has the potential as a novel anticancer agent for HCC.

Objective To evaluate the clinical value of ultrasound - guided percutaneous cinobufagin injection for the treatment of portal vein tumor thrombus (PVTT) in primary liver cancer (PLC) patients. Methods A total of 25 PLC patients with PVTT who were admitted to our hospital from January 2009 to March 2012 were recruited in this study. These patients underwent ultrasound - guided percutaneous cinobufagin injection three times a week, and each course of treatment was 4 - 5 weeks. After treatment, the clinical efficacy and survival rates were determined, and the changes in levels of alpha fetoprotein ( AFP) and alanine aminotransferase ( ALT) were evaluated. Results Seventeen patients showed varying degrees of improvement after treatment, with an overall response rate of 68%. In addition, the levels of AFP and ALT were significantly reduced after treatment (P <0.05). The survival rates at 3, 6, 12, and 24 months after treatment were 88%, 76%, 60%, and 32%, respectively. Conclusion Ultrasound - guided percutaneous cinobufagin injection has good efficacy in the treatment of PVTT in PLC patients and shows a good clinical value. [ABSTRACT FROM AUTHOR]