蛋白质谱分析揭示了3-(2-呋喃甲酰基)-吲哚支架在肝细胞癌中抑制胰岛素样生长因子-1受体（IGF-1R）的潜力。
Protein profiling uncovers IGF-1R inhibition potential of 3-(2-furoyl)-indole scaffolds in hepatocellular carcinoma.
作者信息
Myrsing Efficiency, Mouli H M Chandra, Nikhil Pallaprolu, Sahu Abhishek, Jana Anupam, Ramalingam P
机构信息
Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER), Hajipur, India.
Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, India.
出版信息
Future Med Chem. 2025 Mar;17(5):513-528. doi: 10.1080/17568919.2025.2467616. Epub 2025 Mar 3.
AIM
This study investigates the anti-proliferative potential and possible molecular mechanisms of 3-(2-furoyl)-indole derivatives against HepG2.
METHOD
Identified hit compounds (4a, 4b, 4c) using MTT screening, were further investigated for their efficacy and mechanism of action through FACS studies, in-silico molecular docking, molecular dynamics (MD) simulations, and label-free quantitative proteome and ADMET prediction.
RESULTS
Lead compound 4a, showed IC50 of 27 µM against HepG2 cells and a binding score of -8.077 kcal/mol against IGF-1 R (PDB ID: 5XFS) and formed a stable complex 100 ns. Proteomic study revealed significant downregulation of the IGF-1 R downstream signaling molecules and showed minimal toxicity and favorable drug-like properties.
CONCLUSION
These findings suggest that 4a is a promising IGF-1 R inhibitor and potential drug candidate against drug resistance hepatocellular carcinoma (HCC).
目的
本研究探讨3-(2-呋喃甲酰基)-吲哚衍生物对HepG2细胞的抗增殖潜力及可能的分子机制。
方法
通过MTT筛选鉴定出的活性化合物（4a、4b、4c），进一步通过流式细胞术研究、计算机辅助分子对接、分子动力学（MD）模拟、无标记定量蛋白质组学和ADMET预测来研究其疗效和作用机制。
结果
先导化合物4a对HepG2细胞的IC50为27 μM，对IGF-1 R（PDB ID：5XFS）的结合分数为-8.077 kcal/mol，并形成了100 ns的稳定复合物。蛋白质组学研究显示IGF-1 R下游信号分子显著下调，且毒性极小，具有良好的类药性质。
结论
这些发现表明4a是一种有前景的IGF-1 R抑制剂，是抗耐药性肝细胞癌（HCC）的潜在药物候选物。
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