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<p>Cancer progression involves multiple interconnected signaling pathways, including angiogenesis mediated by VEGFR2 and proliferative signaling regulated by JAK2. Dual inhibition of these kinases represents a promising strategy for anticancer drug development. In this study, an integrated computational approach was employed to evaluate myrcene, a natural monoterpene, as a potential dual VEGFR2/JAK2 inhibitor. Molecular docking results showed that myrcene binds favorably to both targets, with binding affinities of −&#xa0;7.98 ± 0.15&#xa0;kcal/mol against VEGFR2 and − 8.31 ± 0.12&#xa0;kcal/mol against JAK2. These values were compared with standard inhibitors sorafenib (− 6.90 ± 0.18&#xa0;kcal/mol for VEGFR2) and ruxolitinib (− 7.84 ± 0.14&#xa0;kcal/mol for JAK2), indicating that myrcene exhibits stronger predicted binding than both reference compounds under the applied docking conditions. Interactions were primarily stabilized by hydrophobic π-alkyl and π-sigma contacts, with selective hydrogen bonding observed in JAK2. Density functional theory (B3LYP/6-311G(d,p)) confirmed structural stability and a moderate HOMO–LUMO energy gap, suggesting balanced reactivity and stability. In 200-ns molecular dynamics simulations, the VEGFR2–myrcene complex exhibited lower ligand RMSD (1.16&#xa0;Å) and higher hydrogen bond occupancy (2.10) than the JAK2 complex (1.85&#xa0;Å; 1.02), indicating greater dynamic stability for VEGFR2 binding. MM-GBSA calculations further supported favorable binding free energies for both targets (− 26.09&#xa0;kcal/mol for VEGFR2; − 24.00&#xa0;kcal/mol for JAK2), confirming stable complex formation. Collectively, these results suggest that myrcene may serve as a dual VEGFR2/JAK2 inhibitor scaffold with stronger affinity toward VEGFR2 and potential for further anticancer drug development.</p>

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Integrated computational analysis of myrcene as a dual JAK2/VEGFR2 inhibitor for cancer therapy

  • 期刊论文

  • 发表日期：

    2026年6月20日

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  • Cromwel Tepap Zemnou,
  • Ramelle Ngakam

摘要

Cancer progression involves multiple interconnected signaling pathways, including angiogenesis mediated by VEGFR2 and proliferative signaling regulated by JAK2. Dual inhibition of these kinases represents a promising strategy for anticancer drug development. In this study, an integrated computational approach was employed to evaluate myrcene, a natural monoterpene, as a potential dual VEGFR2/JAK2 inhibitor. Molecular docking results showed that myrcene binds favorably to both targets, with binding affinities of − 7.98 ± 0.15 kcal/mol against VEGFR2 and − 8.31 ± 0.12 kcal/mol against JAK2. These values were compared with standard inhibitors sorafenib (− 6.90 ± 0.18 kcal/mol for VEGFR2) and ruxolitinib (− 7.84 ± 0.14 kcal/mol for JAK2), indicating that myrcene exhibits stronger predicted binding than both reference compounds under the applied docking conditions. Interactions were primarily stabilized by hydrophobic π-alkyl and π-sigma contacts, with selective hydrogen bonding observed in JAK2. Density functional theory (B3LYP/6-311G(d,p)) confirmed structural stability and a moderate HOMO–LUMO energy gap, suggesting balanced reactivity and stability. In 200-ns molecular dynamics simulations, the VEGFR2–myrcene complex exhibited lower ligand RMSD (1.16 Å) and higher hydrogen bond occupancy (2.10) than the JAK2 complex (1.85 Å; 1.02), indicating greater dynamic stability for VEGFR2 binding. MM-GBSA calculations further supported favorable binding free energies for both targets (− 26.09 kcal/mol for VEGFR2; − 24.00 kcal/mol for JAK2), confirming stable complex formation. Collectively, these results suggest that myrcene may serve as a dual VEGFR2/JAK2 inhibitor scaffold with stronger affinity toward VEGFR2 and potential for further anticancer drug development.