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通过虚拟筛选方法,针对成胶质细胞瘤的分子药物靶点 FGL2,利用天然化合物。

Targeting FGL2, a molecular drug target for glioblastoma, with natural compounds through virtual screening method.

机构信息

Department of Biological Sciences, College of Natural Sciences, Kongju National University, Gongju, 32588, Republic of Korea.

出版信息

Future Med Chem. 2021 May;13(9):805-816. doi: 10.4155/fmc-2020-0331. Epub 2021 Apr 6.

DOI:10.4155/fmc-2020-0331
PMID:33821685
Abstract

Fibroleukin-2 protein (FGL2) causes redevelopment of brain tumors. Inhibition of these proteins has shown to improve glioblastoma prognosis and treatment efficacy. The current study gathered recently exploited natural compounds that suppress glioblastoma proliferation , tested against FGL2 protein. Twenty-five compounds were explored through a virtual screening platform. Three natural compounds (betanine, hesperetin and ovatodiolide) hit the active site of FGL2. Furthermore, the influence of these compounds was also assessed using gene expression, and ADMET tools showed downregulation of some genes, which caused rapid tumor development while possessing a moderate acute toxicity and pharmacokinetic profile. Our study presents three compounds that are good candidates for evaluation in FGL2 mutated glioblastoma animal models.

摘要

纤维白细胞素-2 蛋白(FGL2)可导致脑肿瘤的重新发展。抑制这些蛋白质已被证明可以改善胶质母细胞瘤的预后和治疗效果。本研究收集了最近开发的天然化合物,这些化合物可以抑制胶质母细胞瘤的增殖,并针对 FGL2 蛋白进行了测试。通过虚拟筛选平台对 25 种化合物进行了探索。三种天然化合物(甜菜碱、橙皮苷和卵形菌内酯)击中了 FGL2 的活性部位。此外,还使用基因表达评估了这些化合物的影响,ADMET 工具显示,一些导致肿瘤快速发展的基因被下调,而这些化合物具有中度的急性毒性和药代动力学特征。我们的研究提出了三种化合物,它们是在 FGL2 突变型胶质母细胞瘤动物模型中进行评估的良好候选物。

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