| 引用本文: | 刘天一,胡雪姣,张哲,胡清洋,闫文欣,东雪,李中.靶向ALK儿童神经母细胞瘤治疗药物的筛选与验证[J].中国现代应用药学,2024,41(24):. |
| liu tianyi,Hu xuejiao,Zhang zhe,Hu qingyang,Yan wenxin,Dong xue,Li zhong.Screening and Verification of Therapeutic Drugs Targeting ALK in Childhood Neuroblastoma[J].Chin J Mod Appl Pharm(中国现代应用药学),2024,41(24):. |
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| 摘要: |
| 摘要：目的 寻找治疗神经母细胞瘤（NB）的有效候选药物，以靶向 ALK 为方向。方法 借助进行计算机辅助药物的虚拟筛选，运用 E-药效团方法挑出潜在结合亲和力的化合物，通过分子动力学模拟测试结合能力，开展 CCK-8 实验验证化合物对NB细胞的杀伤作用，进行 Western blot 实验检测对靶点的抑制作用。结果 通过虚拟筛选和分子动力学模拟，6 种命中化合物中 Quercetagetin效果突出。体外细胞实验表明Quercetagetin能抑制 ALK 表达、诱导神经母细胞瘤细胞凋亡并对NB细胞有杀伤作用。结论 Quercetagetin 可能是治疗 NB 的有效候选药物。 |
| 关键词: ALK 神经母细胞瘤 计算机辅助药物设计 分子动力学模拟 |
| DOI： |
| 分类号:R965.2?????? |
| 基金项目:大连市科技创新基金 |
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| Screening and Verification of Therapeutic Drugs Targeting ALK in Childhood Neuroblastoma |
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liu tianyi1,2,3, Hu xuejiao4, Zhang zhe1,2,3, Hu qingyang4, Yan wenxin4, Dong xue4, Li zhong1,2,3
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1.Dalian Women and Children'2.'3.s Medical Group;4.Dalian Medical University
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| Abstract: |
| ABSTRACT: OBJECTIVE To find an effective candidate drug for the treatment of neuroblastoma (NB) by targeting ALK. METHODS With the help of virtual screening of computer-aided drugs, the E-pharmacophore method was used to select compounds with potential binding affinity. Molecular dynamics simulation was used to test the binding ability. The CCK-8 experiment was carried out to verify the killing effect of compounds on NB cells. Western blot experiment was performed to detect the inhibitory effect on the target. RESULTS Through virtual screening and molecular dynamics simulation, Quercetagetin among the six hit compounds had outstanding effects. In vitro cell experiments showed that Quercetagetin can inhibit ALK expression, induce apoptosis of neuroblastoma cells and have a killing effect on NB cells. CONCLUSION Quercetagetin may be an effective candidate drug for the treatment of NB. |
| Key words: ALK neuroblastoma computer aided drug design molecular dynamics simulation |
