Scholarlink

<p>Lung cancer, especially non-small cell lung carcinoma, remains a leading cause of cancer mortality worldwide. This study integrates multi-layer computational approaches including phytochemical target mapping, expression and survival analytics, structure-based docking, and molecular dynamic simulations to uncover and prioritize bioactive phytochemicals from <i>Caesalpinia bonduc</i> with therapeutic potential. Following drug-likeness and oral-bioavailability filtering, 18 candidate compounds were mapped to 414 lung cancer-associated targets. Protein–protein interaction network and enrichment analysis revealed central hubs within PI3K/MAPK signaling and oncogenic survival pathways (e.g., PIK3CA, MAPK1/3, HRAS), which also exhibited differential expression and prognostic relevance in lung adenocarcinoma datasets. Molecular docking identified rutin as a top candidate, showing the strongest predicted binding to HRAS (− 10.9&#xa0;kcal/mol) and MAPK3 (− 10.4&#xa0;kcal/mol), supported by molecular dynamic simulations indicating stable pocket engagement. These findings position rutin as a multi-target modulator capable of attenuating proliferative and survival signaling through upstream and effector nodes. Despite computational limitations, including predictive target inference, docking approximations, and limited dynamic sampling, the convergent in-silico evidence forms a solid foundation for experimental validation. Proposed follow-up includes in-vitro assays assessing viability, pathway biomarkers, and genetic perturbation strategies, coupled with biophysical binding measurements and pharmacokinetic profiling. In summary, this integrated study provides mechanistically grounded, atomistic support for rutin’s prioritized advancement toward preclinical validation against key components of the PI3K/MAPK axis and HRAS in lung cancer.</p> Graphical Abstract <p>This graphical abstract depicts the flow of the overall experimental design as well as the results produced from this study</p> <p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Characterization of rutin bindingto HRAS and MAPK3 and its clinical prognostic relevancein lung cancer: Using in silico and clinical prognostic experimental design

  • 期刊论文

  • 发表日期：

    2025年9月29日

查看全文
  • Hossam Kamli

摘要

Lung cancer, especially non-small cell lung carcinoma, remains a leading cause of cancer mortality worldwide. This study integrates multi-layer computational approaches including phytochemical target mapping, expression and survival analytics, structure-based docking, and molecular dynamic simulations to uncover and prioritize bioactive phytochemicals from Caesalpinia bonduc with therapeutic potential. Following drug-likeness and oral-bioavailability filtering, 18 candidate compounds were mapped to 414 lung cancer-associated targets. Protein–protein interaction network and enrichment analysis revealed central hubs within PI3K/MAPK signaling and oncogenic survival pathways (e.g., PIK3CA, MAPK1/3, HRAS), which also exhibited differential expression and prognostic relevance in lung adenocarcinoma datasets. Molecular docking identified rutin as a top candidate, showing the strongest predicted binding to HRAS (− 10.9 kcal/mol) and MAPK3 (− 10.4 kcal/mol), supported by molecular dynamic simulations indicating stable pocket engagement. These findings position rutin as a multi-target modulator capable of attenuating proliferative and survival signaling through upstream and effector nodes. Despite computational limitations, including predictive target inference, docking approximations, and limited dynamic sampling, the convergent in-silico evidence forms a solid foundation for experimental validation. Proposed follow-up includes in-vitro assays assessing viability, pathway biomarkers, and genetic perturbation strategies, coupled with biophysical binding measurements and pharmacokinetic profiling. In summary, this integrated study provides mechanistically grounded, atomistic support for rutin’s prioritized advancement toward preclinical validation against key components of the PI3K/MAPK axis and HRAS in lung cancer.

Graphical Abstract

This graphical abstract depicts the flow of the overall experimental design as well as the results produced from this study