School of Pharmacy, Xi'an Jiaotong University, 76# Yanta West Road, Xi'an 710061, China; Institute of Pharmaceutical Science and Technology, Western China Science & Technology Innovation Harbour, Xi'an 710115, China.
School of Pharmacy, Xi'an Jiaotong University, 76# Yanta West Road, Xi'an 710061, China; Institute of Pharmaceutical Science and Technology, Western China Science & Technology Innovation Harbour, Xi'an 710115, China.
J Pharm Biomed Anal. 2024 Jan 20;238:115816. doi: 10.1016/j.jpba.2023.115816. Epub 2023 Oct 26.
The SNAP-tag-epidermal growth factor receptor (SNAP-tag-EGFR) cell membrane chromatography (CMC) model is a powerful tool for investigating ligand-receptor interactions and screening active ingredients in traditional Chinese medicine. Most tyrosine kinase inhibitors (TKIs) target epidermal growth factor receptors. However, TKIs associated with significant side effects and drug resistance must be addressed immediately. Therefore, there is an urgent need to develop new TKIs with high efficiency and low toxicity. Because of its low toxicity and side effects, traditional Chinese medicine has been widely employed to treat various diseases, including cancer. Hence, this study aimed to use the SNAP-tag-EGFR/CMC-high-performance liquid chromatography-mass spectrometry (HPLC-MS) two-dimensional system model as the research tool to screen and identify potential EGFR antagonists from the Chinese medicine Silybum marianum (L.) Gaertn. The applicability of the system was verified using the positive control drug osimertinib. Four potential EGFR antagonists were screened from the Chinese medicine Silybum marianum (L.) Gaertn.. They were identified as silydianin, silychristin, silybin, and isosilybin. Additionally, their pharmacological activity was preliminarily verified using a CCK-8 assay. The kinetic parameters of the four active ingredients interacting with EGFR and their binding modes with EGFR were analyzed using nonlinear chromatography (NLC) and molecular docking. This study identified silydianin, silychristin, silybin, and isosilybin from Silybum marianum (L.) Gaertn. and verified their potential antitumor effects on EGFR.
SNAP 标签-表皮生长因子受体（SNAP-tag-EGFR）细胞膜色谱（CMC）模型是研究配体-受体相互作用和筛选中药有效成分的有力工具。大多数酪氨酸激酶抑制剂（TKI）靶向表皮生长因子受体。然而，与显著副作用和耐药性相关的 TKI 必须立即得到解决。因此，迫切需要开发高效低毒的新型 TKI。由于中药的低毒性和副作用，它已被广泛用于治疗各种疾病，包括癌症。因此，本研究旨在使用 SNAP-tag-EGFR/CMC-高效液相色谱-质谱（HPLC-MS）二维系统模型作为研究工具，从中药水飞蓟（L.）Gaertn. 中筛选和鉴定潜在的 EGFR 拮抗剂。使用阳性对照药物奥希替尼验证了该系统的适用性。从中药水飞蓟（L.）Gaertn. 中筛选出 4 种潜在的 EGFR 拮抗剂。它们被鉴定为水飞蓟宁、水飞蓟宾、水飞蓟素和异水飞蓟素。此外，还使用 CCK-8 测定法初步验证了它们的药理活性。使用非线性色谱（NLC）和分子对接分析了四种活性成分与 EGFR 相互作用的动力学参数及其与 EGFR 的结合模式。本研究从水飞蓟（L.）Gaertn. 中鉴定出水飞蓟宁、水飞蓟宾、水飞蓟素和异水飞蓟素，并验证了它们对 EGFR 的潜在抗肿瘤作用。
