Juntao Wang

Salidroside has been reported to have various pharmacological activities, including hypoxia tolerance, anti‐radiation, and antitumor. In this study, we studied the antitumor activity of salidroside ether derivatives in the human hepatocellular carcinoma cell line Hep3B. We created eleven new benzyl halide derivatives called S1–S11 by modifying the phenolic hydroxyl groups at the C4 position of salidroside. The compounds were shown to inhibit tumor proliferation in the in vitro CCK‐8 assay. Compounds S4, S5, S6, S7, S8, and S11 demonstrated strong inhibitory activity anti‐human hepatic cancer cell Hep3B, with IC₅₀ values of 67.89, 97.55, 73.67, 57.92, 88.29, and 33.39 μM, respectively. Under the inverted microscope, compared with the blank group, after 48 h of administration, it showed obvious proliferation inhibition and apoptosis characteristics. In addition, network pharmacology predicts that these derivatives may have the effect of regulating the nervous system and protecting neuronal cells without violating Lipinski's Rule. In summary, the benzyl halide modification on the C4 phenolic hydroxyl group on the benzene ring of SAL can improve its antitumor activity, which provides ideas for the subsequent development of salidroside antitumor drugs.

The asialoglycoprotein receptor 1 (ASGR1) represents a highly promising target for drug development, with its expression regulation closely linked to various diseases. Consequently, research concentrating on targeted therapies against ASGR1 holds significant importance in devising effective treatment strategies. In this study, we utilized the CRISPR-Knockin technology to insert a firely luciferase reporter gene downstream of exon 9 of the ASGR1 gene in HepG2 cell line. This modification enables the expression level of luciferase to be directly proportional to the activity intensity of the ASGR1 protein. We successfully established a drug screening and evaluation model for ASGR1 and employed it for high-throughput screening of potential inhibitors from a microbial molecular metabolite library. After our screening process, several promising candidates were identified as potential ASGR1 inhibitors. Western blotting experiment was conducted to validate the efficacy of our drug screening model, thereby providing a solid experimental foundation for the development of novel targeted therapeutics targeting ASGR1.