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

Cancer progression involves interconnected pathways, including angiogenesis mediated by VEGFR2 and proliferative signaling regulated by JAK2. Dual inhibition of these kinases represents a promising therapeutic strategy. In this study, we applied an integrated computational approach to evaluate myrcene, a natural monoterpene, as a potential dual JAK2/VEGFR2 inhibitor. Molecular docking revealed favorable binding within the ATP-binding pockets of VEGFR2 and JAK2, with scores of − 7.98 and − 8.31 kcal·mol⁻¹, respectively. 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 gap, supporting dispersion-driven interactions and occasional polar contacts. 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 (RMSD 1.85 Å; hydrogen bonds 1.02), reflecting greater dynamic stability for VEGFR2. MM-GBSA analysis showed strongly favorable binding free energies for both targets (ΔG = − 26.09 kcal·mol⁻¹ for VEGFR2; ΔG = − 24.00 kcal·mol⁻¹ for JAK2), indicating that myrcene can form stable, energetically favorable complexes with both kinases. Collectively, these results support myrcene as a dual inhibitor, with pronounced VEGFR2 affinity and significant JAK2 engagement, highlighting its potential as a scaffold for the rational design of dual-target anticancer therapeutics.