癌症和糖尿病统计数据的意外上升已成为重大的全球威胁，引发了针对各种生物标志物的不断研究，这些标志物可以作为创新的治疗靶点，用于管理这些疾病。最近发现了EZH2-PPARs的调节功能如何影响代谢和信号通路，从而促进了这种疾病，这是一项重大的突破，在GSK-126和贝嘌呤酸等抑制剂的协同作用下，用于治疗这些疾病。然而，并未报告有关参与相关副作用的其他蛋白质生物标志物的发现。由于这项虚拟研究，我们确定了EZH2-PPARs和其他调节胰腺癌和糖尿病病理的蛋白质生物标志物之间的基因疾病关联和蛋白质相互作用网络，ADME/毒性剖析，一些自然产物的配体模拟和密度泛函理论。结果表明，在调查的生物标志物中，肥胖和高血压疾病之间存在相关性。同时，预测的蛋白质网络验证了与癌症和糖尿病的联系，筛选出九种自然产物，具有多种靶点的结合能力。在所有自然产物中，植物内醇A在药物类似性轮廓的体外验证中表现优异，优于标准药物（GSK-126和贝嘌呤酸）。因此，这些自然产物被最终建议进行额外的实验筛选，以补充关于它们在针对EZH2-PPARs的新靶点进行糖尿病和癌症治疗的药物开发方面的实用性结果。©2023年。根据Springer Science+Business Media，LLC的独家许可，属于Springer Nature。

The unexpected rise in cancer and diabetes statistics has been a significant global threat, inciting ongoing research into various biomarkers that can act as innovative therapeutic targets for their management. The recent discovery of how EZH2-PPARs' regulatory function affects the metabolic and signalling pathways contributing to this disease has posed a significant breakthrough, with the synergistic combination of inhibitors like GSK-126 and bezafibrate for treating these diseases. Nonetheless, no findings on other protein biomarkers involved in the associated side effects have been reported. As a result of this virtual study, we identified the gene-disease association, protein interaction networks between EZH2-PPARs and other protein biomarkers regulating pancreatic cancer and diabetes pathology, ADME/Toxicity profiling, docking simulation and density functional theory of some natural products. The results indicated a correlation between obesity and hypertensive disease for the investigated biomarkers. At the same time, the predicted protein network validates the link to cancer and diabetes, and nine natural products were screened to have versatile binding capacity against the targets. Among all natural products, phytocassane A outperforms the standard drugs' (GSK-126 and bezafibrate) in silico validation for drug-likeness profiles. Hence, these natural products were conclusively proposed for additional experimental screening to complement the results on their utility in drug development for diabetes and cancer therapy against the EZH2-PPARs' new target.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.