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HN-N07小分子作为非小细胞肺癌血管生成和淋巴管生成致癌特征抑制剂的计算机模拟评估

In Silico Evaluation of HN-N07 Small Molecule as an Inhibitor of Angiogenesis and Lymphangiogenesis Oncogenic Signatures in Non-Small Cell Lung Cancer.

作者信息

Chen Lung-Ching, Mokgautsi Ntlotlang, Kuo Yu-Cheng, Wu Alexander T H, Huang Hsu-Shan

机构信息

Division of Cardiology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 11101, Taiwan.

School of Medicine, Fu Jen Catholic University, New Taipei 24205, Taiwan.

出版信息

Biomedicines. 2023 Jul 17;11(7):2011. doi: 10.3390/biomedicines11072011.

Abstract

Tumor angiogenesis and lymphangiogenesis pathways have been identified as important therapeutic targets in non-small cell lung cancer (NSCLC). Bevacizumab, which is a monoclonal antibody, was the initial inhibitor of angiogenesis and lymphangiogenesis that received approval for use in the treatment of advanced non-small cell lung cancer (NSCLC) in combination with chemotherapy. Despite its usage, patients may still develop resistance to the treatment, which can be attributed to various histological subtypes and the initiation of treatment at advanced stages of cancer. Due to their better specificity, selectivity, and safety compared to chemotherapy, small molecules have been approved for treating advanced NSCLC. Based on the development of multiple small-molecule antiangiogenic drugs either in house and abroad or in other laboratories to treat NSCLC, we used a quinoline-derived small molecule-HN-N07-as a potential target drug for NSCLC. Accordingly, we used computational simulation tools and evaluated the drug-likeness properties of HN-N07. Moreover, we identified target genes, resulting in the discovery of the target pro-angiogenic genes. Furthermore, we used in silico molecular docking analysis to determine whether HN-N07 could potentially inhibit . Interestingly, the results of docking HN-N07 with the , and oncogenes revealed unique binding affinities, which were significantly higher than those of standard inhibitors. In summary, these results indicate that HN-N07 shows promise as a potential inhibitor of oncogenic signaling pathways in NSCLC. Ongoing studies that involve in vitro experiments and in vivo investigations using tumor-bearing mice are in progress, aiming to evaluate the therapeutic effectiveness of the HN-N07 small molecule.

摘要

肿瘤血管生成和淋巴管生成途径已被确定为非小细胞肺癌(NSCLC)的重要治疗靶点。贝伐单抗是一种单克隆抗体,是首个获批用于联合化疗治疗晚期非小细胞肺癌(NSCLC)的血管生成和淋巴管生成抑制剂。尽管使用了该药物,但患者仍可能对治疗产生耐药性,这可能归因于各种组织学亚型以及癌症晚期开始治疗。由于小分子与化疗相比具有更好的特异性、选择性和安全性,已获批用于治疗晚期NSCLC。基于国内外或其他实验室开发的多种治疗NSCLC的小分子抗血管生成药物,我们使用了一种喹啉衍生的小分子——HN-N07——作为NSCLC的潜在靶向药物。因此,我们使用了计算模拟工具并评估了HN-N07的类药性质。此外,我们确定了靶基因,从而发现了促血管生成靶基因。此外,我们使用计算机辅助分子对接分析来确定HN-N07是否可能抑制。有趣的是,将HN-N07与、和癌基因进行对接的结果显示出独特的结合亲和力,显著高于标准抑制剂。总之,这些结果表明HN-N07有望成为NSCLC致癌信号通路的潜在抑制剂。目前正在进行涉及体外实验和使用荷瘤小鼠进行体内研究的实验,旨在评估HN-N07小分子的治疗效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2953/10376976/bb283071350c/biomedicines-11-02011-g001.jpg

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