{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T04:29:21Z","timestamp":1783744161869,"version":"3.55.0"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T00:00:00Z","timestamp":1749427200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Papillary thyroid carcinoma (PTC) is the most prevalent type of thyroid cancer, with aggressive variants presenting major therapeutic challenges. Vascular endothelial growth factor receptor-2 (VEGFR-2) is a key regulator of tumor angiogenesis and is highly expressed in PTC, making it a promising target for therapeutic intervention. This highlights the potential of VEGFR-2 inhibition as an effective strategy for managing PTC. In this study, we employed virtual drug screening, molecular dynamics simulations, and binding free energy calculations to identify potential VEGFR-2 inhibitors from the African natural product database (AfroDb). Our virtual drug screening identified three lead compounds SA_0090, 17.3.1.7.8 and BMC_0005 with a docking scores of \u22129.04\u00a0kcal\/mol, \u22128.96\u00a0kcal\/mol, and \u22128.33\u00a0kcal\/mol respectively, surpassing the control compound (\u22128.39\u00a0kcal\/mol). Molecular dynamics simulation analysis confirmed the dynamic stability, structural compactness, and minimal residual fluctuations of the 17.3.1.7.8 and BMC_0005 compounds-VEGFR2 complexes. The binding free energy calculations further supported the strong interactions, with values recorded as \u221260.3861 \u00b1 0.39\u00a0kcal\/mol for the control, \u221252.2732 \u00b1 0.37\u00a0kcal\/mol for SA_0090, \u221252.7797 \u00b1 0.62\u00a0kcal\/mol for 17.3.1.7.8, and \u221261.476 \u00b1 0.59\u00a0kcal\/mol for BMC_0005. Additionally, the selected compounds exhibited highly favorable ADMET properties, including optimal water solubility, efficient gastrointestinal absorption, and a non-hepatotoxic profile, all aligning with Lipinski\u2019s rule of five. In conclusion, these findings highlight 17.3.1.7.8 and BMC_0005 compounds as compelling candidates for VEGFR-2 inhibition, offering a promising therapeutic avenue for papillary thyroid carcinoma, warranting further <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> validation for potential therapeutic use.<\/jats:p>","DOI":"10.3389\/fphar.2025.1583329","type":"journal-article","created":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T05:24:43Z","timestamp":1749446683000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Structure-based molecular screening and dynamic simulation of phytocompounds targeting VEGFR-2: a novel therapeutic approach for papillary thyroid carcinoma"],"prefix":"10.3389","volume":"16","author":[{"given":"Shuai","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingqian","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjun","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiong","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Mei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weidong","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijie","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,6,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1016\/j.ipha.2023.11.010","article-title":"Molecular docking studies of some benzoxazole and benzothiazole derivatives as VEGFR-2 target inhibitors: in silico design, MD simulation, pharmacokinetics and DFT studies","volume":"2","author":"Abdullahi","year":"2024","journal-title":"Intell. 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