Jia Wenqing, Cheng Xianchao
College of Chemistry and Chemical Engineering, Qilu Normal University, Jinan 250200, China.
Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300070, China.
Int J Mol Sci. 2025 Apr 10;26(8):3565. doi: 10.3390/ijms26083565.
Head and neck squamous cell carcinoma (HNSCC) remains a major health burden, with abnormal activation of phosphatidylinositol 3-kinase alpha (PI3Kα) strongly implicated in its pathogenesis. Targeting PI3Kα represents a promising therapeutic strategy. In this study, we employed structure-based virtual screening to identify natural small-molecule inhibitors of PI3Kα. A total of 12,800 molecules were screened, and five compounds were selected for further evaluation based on binding affinity and interaction patterns. Pharmacokinetic properties were assessed using ADMET predictions, and molecular dynamics (MD) simulations were conducted to validate the binding stability. Among the candidates, Apigetrin demonstrated favorable ADMET properties, a high safety profile, and stable binding within the ATP-binding pocket of PI3Kα. These findings suggest that Apigetrin is a promising natural PI3Kα inhibitor with potential therapeutic relevance for HNSCC.
头颈部鳞状细胞癌（HNSCC）仍然是一项重大的健康负担，磷脂酰肌醇3-激酶α（PI3Kα）的异常激活与其发病机制密切相关。靶向PI3Kα是一种很有前景的治疗策略。在本研究中，我们采用基于结构的虚拟筛选来鉴定PI3Kα的天然小分子抑制剂。共筛选了12800个分子，并根据结合亲和力和相互作用模式选择了5种化合物进行进一步评估。使用ADMET预测评估药代动力学性质，并进行分子动力学（MD）模拟以验证结合稳定性。在候选物中，芹菜素表现出良好的ADMET性质、高安全性概况以及在PI3Kα的ATP结合口袋内的稳定结合。这些发现表明，芹菜素是一种有前景的天然PI3Kα抑制剂，对HNSCC具有潜在的治疗意义。
