MDM2 是一种编码参与细胞存活、生长和 DNA 修复的蛋白质的基因。它与胶质母细胞瘤（GBM）的发生和进展有关。抑制 MDM2-p53 相互作用已成为治疗 GBM 的一种有前景的策略。在这项研究中，我们对不同的数据集进行了全面的转录组表达分析，并观察到部分 GBM 病例中 MDM2 过度表达。 MDM2 负向调节主要肿瘤抑制因子 p53。 MDM2 和 p53 之间的相互作用是癌症治疗的一个有希望的靶标，因为它可以响应不同的应激条件（例如癌基因激活或 DNA 损伤）而触发 p53 介导的细胞死亡。在这项研究中，我们确定了基于肽的 MDM2 抑制作为 GBM 的治疗策略。我们使用分子结构动力学方法进一步验证了 MDM2-肽相互作用的稳定性。主要轨迹，包括均方根偏差（RMSD）、均方根波动（RMSF）和回转半径（RoG），表明候选肽与天然配体和对照药物相比具有更稳定的结合。通过 MMGBSA 分析进一步评估了结合相互作用的稳定性，这也表明 MDM2 与两种肽分子具有稳定的结合。基于这些结果，可以进一步测试肽 P-1843 和 P-3837 进行实验验证，以确认它们对 MDM-2 的靶向抑制作用。这种方法可以提供一种高度选择性和高效的抑制剂，与基于药物的小分子相比，其副作用和毒性可能更少。版权所有 © 2024。由 Elsevier Inc. 出版。

MDM2 is a gene that encodes a protein involved in cell survival, growth, and DNA repair. It has been implicated in the development and progression of glioblastoma (GBM). Inhibition of the MDM2-p53 interaction has emerged as a promising strategy for treating GBM. In this study, we performed comprehensive transcriptomic expression analysis from diverse datasets and observed MDM2 overexpression in a subset of GBM cases. MDM2 negatively regulates the major onco-suppressor p53. The interaction between MDM2 and p53 is a promising target for cancer therapy, as it can trigger p53-mediated cell death in response to different stress conditions, such as oncogene activation or DNA damage. In this study, we have identified a peptide-based inhibition of MDM2 as a therapeutic strategy for GBM. We have further validated the stability of the MDM2-peptide interaction using a molecular structural dynamics approach. The major trajectories, including root mean square of deviation (RMSD), root mean square of fluctuation (RMSF), and radius of gyration (RoG), indicate that the candidate peptides have a more stable binding compared to the native ligand and control drug. The stability of the binding interaction was further estimated by MMGBSA analysis, which also suggests that MDM2 has a stable binding with both peptide molecules. Based on these results, peptides P-1843 and P-3837 could be tested further for experimental validation to confirm their targeted inhibition of MDM-2. This approach could provide a highly selective and efficient inhibitor with potentially fewer side effects and less toxicity compared to small drug-based molecules.Copyright © 2024. Published by Elsevier Inc.