{"title":"In Silico Study of Micheliolide Derivatives as Potential Non-Small Cell Lung Cancer Drugs Targeting the Epidermal Growth Factor Receptor.","authors":"Sahat Halim, Aziza Harris, Steffi Cong Andi Nata, Achmad Mudassir Muchlis, - Darmadi, Herikurniawan Herikurniawan, Cleopas Martin Rumende","doi":"10.31557/APJCP.2026.27.9.3265","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>To identify Micheliolide-based derivatives with favorable drug-like properties and inhibitory potential against the epidermal growth factor receptor (EGFR) using an integrated in silico approach.</p><p><strong>Methods: </strong>Micheliolide derivatives were evaluated for pharmacokinetic and toxicity profiles using SwissADME and ADMET-AI, and anticancer-related activity was predicted using PASS Online. Molecular docking was performed with AutoDock Vina using erlotinib as a reference ligand. The top-ranked compounds were further examined through 50 ns molecular dynamics simulations to assess complex stability.</p><p><strong>Results: </strong>All derivatives fulfilled Lipinski's criteria. Several compounds demonstrated favorable predicted bioavailability and anticancer probability. Docking analysis identified compound 10 as having the strongest binding affinity, followed by compounds 19 and 3, with all three occupying the same EGFR binding pocket as erlotinib. Molecular dynamics simulations showed that compounds 3 and 19 formed more stable complexes, maintaining root-mean-square deviation values of approximately 1-3 Å throughout the trajectory, whereas compound 10 displayed greater fluctuations and reduced stability.</p><p><strong>Conclusion: </strong>Compounds 3 and 19 exhibited the most favorable combination of binding affinity, dynamic stability, and predicted safety profiles, highlighting their potential as lead candidates for further development as EGFR inhibitors in NSCLC.</p>","PeriodicalId":55451,"journal":{"name":"Asian Pacific Journal of Cancer Prevention","volume":"27 9","pages":"3265-3272"},"PeriodicalIF":0.0000,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Asian Pacific Journal of Cancer Prevention","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.31557/APJCP.2026.27.9.3265","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"Medicine","Score":null,"Total":0}
引用次数: 0
Abstract
Objective: To identify Micheliolide-based derivatives with favorable drug-like properties and inhibitory potential against the epidermal growth factor receptor (EGFR) using an integrated in silico approach.
Methods: Micheliolide derivatives were evaluated for pharmacokinetic and toxicity profiles using SwissADME and ADMET-AI, and anticancer-related activity was predicted using PASS Online. Molecular docking was performed with AutoDock Vina using erlotinib as a reference ligand. The top-ranked compounds were further examined through 50 ns molecular dynamics simulations to assess complex stability.
Results: All derivatives fulfilled Lipinski's criteria. Several compounds demonstrated favorable predicted bioavailability and anticancer probability. Docking analysis identified compound 10 as having the strongest binding affinity, followed by compounds 19 and 3, with all three occupying the same EGFR binding pocket as erlotinib. Molecular dynamics simulations showed that compounds 3 and 19 formed more stable complexes, maintaining root-mean-square deviation values of approximately 1-3 Å throughout the trajectory, whereas compound 10 displayed greater fluctuations and reduced stability.
Conclusion: Compounds 3 and 19 exhibited the most favorable combination of binding affinity, dynamic stability, and predicted safety profiles, highlighting their potential as lead candidates for further development as EGFR inhibitors in NSCLC.
期刊介绍：
Cancer is a very complex disease. While many aspects of carcinoge-nesis and oncogenesis are known, cancer control and prevention at the community level is however still in its infancy. Much more work needs to be done and many more steps need to be taken before effective strategies are developed. The multidisciplinary approaches and efforts to understand and control cancer in an effective and efficient manner, require highly trained scientists in all branches of the cancer sciences, from cellular and molecular aspects to patient care and palliation.
The Asia Pacific Organization for Cancer Prevention (APOCP) and its official publication, the Asia Pacific Journal of Cancer Prevention (APJCP), have served the community of cancer scientists very well and intends to continue to serve in this capacity to the best of its abilities. One of the objectives of the APOCP is to provide all relevant and current scientific information on the whole spectrum of cancer sciences. They aim to do this by providing a forum for communication and propagation of original and innovative research findings that have relevance to understanding the etiology, progression, treatment, and survival of patients, through their journal. The APJCP with its distinguished, diverse, and Asia-wide team of editors, reviewers, and readers, ensure the highest standards of research communication within the cancer sciences community across Asia as well as globally.
The APJCP publishes original research results under the following categories:
-Epidemiology, detection and screening.
-Cellular research and bio-markers.
-Identification of bio-targets and agents with novel mechanisms of action.
-Optimal clinical use of existing anti-cancer agents, including combination therapies.
-Radiation and surgery.
-Palliative care.
-Patient adherence, quality of life, satisfaction.
-Health economic evaluations.
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