Li Guojun, Chen Jionghuang, Chen Rui, Yu Weihua
Department of General Surgery, Shangyu People's Hospital of Shaoxing, Shaoxing University, Shaoxing, China.
Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
PLoS One. 2025 May 14;20(5):e0323699. doi: 10.1371/journal.pone.0323699. eCollection 2025.
This study focuses on the development and optimization of S11a-0000168202, a novel LIMK1 inhibitor with potential therapeutic applications in gastric cancer. Through scaffold hopping and structural modification of HIT100844099, S11a-0000168202 demonstrated enhanced binding stability and stronger interactions with key LIMK1 residues, including GLU-414, ILE-416, and HIS-464. Molecular dynamics simulations and MMGBSA analyses confirmed the compound's stability, while ADMET evaluation revealed favorable properties such as moderate lipophilicity, good human intestinal absorption, and low P-glycoprotein inhibition. Despite the promising computational results, the lack of experimental validation remains a limitation. Future studies should focus on in vitro and in vivo testing to confirm S11a-0000168202's efficacy, pharmacokinetics, and safety. This compound holds significant potential as a therapeutic agent for LIMK1-targeted gastric cancer treatment.
本研究聚焦于S11a - 0000168202的开发与优化，这是一种新型LIMK1抑制剂，在胃癌治疗中具有潜在的治疗应用价值。通过对HIT100844099进行骨架跃迁和结构修饰，S11a - 0000168202表现出增强的结合稳定性以及与关键LIMK1残基（包括GLU - 414、ILE - 416和HIS - 464）更强的相互作用。分子动力学模拟和MMGBSA分析证实了该化合物的稳定性，而ADMET评估揭示了其具有适度亲脂性、良好的人体肠道吸收性和低P - 糖蛋白抑制等良好性质。尽管计算结果很有前景，但缺乏实验验证仍是一个限制因素。未来的研究应集中于体外和体内测试，以确认S11a - 0000168202的疗效、药代动力学和安全性。这种化合物作为针对LIMK1的胃癌治疗药物具有巨大的潜力。
