ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Experimental Pharmacology and Drug Discovery
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1605515
This article is part of the Research TopicOrganoids for Drug DiscoveryView all 11 articles
A diaryl urea derivative, SMCl inhibits cell proliferation through the RAS/RAF/MEK/ERK pathway in hepatocellular carcinoma
Provisionally accepted
- 1School of Pharmacy, Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong Province, China
- 2College of Pharmacy, Shenzhen Technology University, Shenzhen, China
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Introduction: Hepatocellular carcinoma (HCC) ranks among the three most prevalent cancer-related diseases in terms of incidence. Hence, exploring drugs for HCC therapy is of great significance. Compounds with a diaryl urea structure have been reported to exhibit a broad range of biological activities, including anticancer activity. This study focuses on the specific diaryl urea derivative 4-(4-(3-(2-chloro-3-(trifluoromethyl)phenyl)ureido)phenoxy)-N-methylpicolinamide (SMCl), with particular emphasis on investigating its therapeutic effects against hepatocellular carcinoma (HCC) and elucidating the underlying molecular mechanisms. Methods: In vitro anti-cancer effects of SMCl were evaluated in HCC cell lines using MTS, colony formation, and wound healing assays. Western blot analyzed RAS/RAF/MEK/ERK pathway modulation. In vivo efficacy was assessed using a xenograft model. Results: The MTS and colony formation assays demonstrated that SMCl significantly decreased the viability of HCC cells. Western blot analysis demonstrated that SMCl effectively suppressed hepatocellular carcinoma proliferation by markedly inhibiting the RAS/RAF/MEK/ERK signaling pathway, with this inhibitory effect exhibiting both time-and concentration-dependent characteristics. SMCl also demonstrated significant therapeutic efficacy in the xenograft tumor model, achieving a tumor inhibition rate of 72.37%. Notably, it showed no significant impact on spleen weight or body weight in mice, indicating low toxicity to normal tissues Conclusion: This study first elucidates the effects of SMCl on HCC cells and its impact on the RAS/RAF/MEK/ERK signaling pathway, providing a potential active compound for the clinical treatment of liver cancer.
Keywords: Hepatocellular Carcinoma, diaryl urea derivative, Cell Proliferation, RAS/RAF/MEK/ERK, Bioactive compound
Received: 03 Apr 2025; Accepted: 27 Jun 2025.
Copyright: © 2025 Fu, Fang, Zhu, Qiu, Lai, Xu, Chen and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Xiaohui Zhu, College of Pharmacy, Shenzhen Technology University, Shenzhen, China
Yang Li, College of Pharmacy, Shenzhen Technology University, Shenzhen, China
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