Li Xiuying, Ruan Pinglang, Jiang Gang, Zhang Weidong
Pulmonary and Critical Care Medicine, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan, China.
Department of Dermatology, Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Medical Epigenomics, Changsha, Hunan, China.
Anticancer Agents Med Chem. 2025;25(8):555-562. doi: 10.2174/1871520623666230403104816.
Tyrosine kinases have emerged as key stimulatory drivers in several cancer-related pathways. This is particularly evident in non-small cell lung cancer with regulating cell growth and apoptosis and so on. Tyrosine kinase inhibitors (TKI) are one breakthrough option that could improve the life quality of cancer patients.
This study aims to find more effective tyrosine kinase inhibitors.
In this study, natural products from TargetMol that may be the potential TKI for lung cancer were screened through structure-based virtual screening and experimental validation. Moreover, the binding between the hit compounds and tyrosine kinase was explored.
From the study findings, Gramicidin and Tannic acid have strong interactions with the four tyrosine kinases (ALK, TRK, MET, and ABL), and this could significantly inhibit the viability of A549 cells in a concentrationdependent manner.
These findings indicated that Gramicidin and Tannic acid might be potential multiple TKI and are promising anticancer agents that call for further study.
酪氨酸激酶已成为多种癌症相关信号通路中的关键刺激驱动因子。这在非小细胞肺癌中尤为明显，它可调节细胞生长、凋亡等。酪氨酸激酶抑制剂（TKI）是一种能够改善癌症患者生活质量的突破性选择。
本研究旨在寻找更有效的酪氨酸激酶抑制剂。
在本研究中，通过基于结构的虚拟筛选和实验验证，从TargetMol筛选出可能是肺癌潜在TKI的天然产物。此外，还探究了命中化合物与酪氨酸激酶之间的结合情况。
从研究结果来看，短杆菌肽和单宁酸与四种酪氨酸激酶（ALK、TRK、MET和ABL）有强烈相互作用，且能以浓度依赖的方式显著抑制A549细胞的活力。
这些发现表明，短杆菌肽和单宁酸可能是潜在的多靶点TKI，是有前景的抗癌药物，值得进一步研究。
