Ngernsombat Chawalit, Suriya Utid, Prattapong Pongphol, Verma Kanika, Rungrotmongkol Thanyada, Soonkum Thananya, Kuhaudomlarp Sakonwan, Janvilisri Tavan
Graduate Program in Molecular Medicine, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand.
Division of Biochemistry, Department of Preclinical Science, Faculty of Medicine, Thammasat University, Pathumthani, 12120, Thailand.
Sci Rep. 2024 Dec 28;14(1):31461. doi: 10.1038/s41598-024-82967-7.
Wnt signaling is a critical pathway implicated in cancer development, with Frizzled proteins, particularly FZD10, playing key roles in tumorigenesis and recurrence. This study focuses on the potential of repurposed FDA-approved drugs targeting FZD10 as a therapeutic strategy for nasopharyngeal carcinoma (NPC). The tertiary structure of human FZD10 was constructed using homology modeling, validated by Ramachandran plot and ProQ analysis. Virtual screening of 1,094 FDA-approved drugs identified 17 potential inhibitors, with prazosin, rilpivirine, doxazosin, and nicergoline demonstrating significant cytotoxicity against NPC cells. Further molecular dynamics simulations and binding energy analyses confirmed the stable binding of these drugs to FZD10. The results suggest that these repurposed drugs could serve as promising candidates for targeted NPC therapy, warranting further investigation.
Wnt信号通路是一条与癌症发展相关的关键通路，卷曲蛋白，特别是FZD10，在肿瘤发生和复发中起关键作用。本研究聚焦于重新利用美国食品药品监督管理局（FDA）批准的针对FZD10的药物作为鼻咽癌（NPC）治疗策略的潜力。使用同源建模构建人FZD10的三级结构，并通过拉氏图和ProQ分析进行验证。对1094种FDA批准的药物进行虚拟筛选，确定了17种潜在抑制剂，其中哌唑嗪、利匹韦林、多沙唑嗪和尼麦角林对NPC细胞表现出显著的细胞毒性。进一步的分子动力学模拟和结合能分析证实了这些药物与FZD10的稳定结合。结果表明，这些重新利用的药物有望成为NPC靶向治疗的候选药物，值得进一步研究。
