Voacangine specifically and directly binds to vascular endothelial growth factor receptor 2 (VEGFR2) (a) DARTS results from direct binding of voacangine to various receptor tyrosine kinases (RTKs) in HUVECs. HUVEC lysates were incubated with voacangine and digested with pronase (1 μg/mL) at each incubation time. Each value represents the mean ± S.D. from three independent experiments. ** p < 0.01 versus control, * p < 0.05 versus control. NT: non-treated control, Voa: voacangine-treated, Pro -:Pronase non-treated; Pro +:Pronase treated; -:Non-treated (b) In silico docking analysis using a 2D-diagram for validating the interaction between voacangine and VEGFR2 (juxtamembrane and kinase domains, RCSB Protein Data Bank number: 4AGD). Left panel, green (voacangine) is superimposed with VEGFR2 (grey). Right panel, binding motifs are illustrated with various interactions of voacangine with the ATP-binding pocket of VEGFR2. (c) Effect of voacangine on VEGF-induced VEGFR2 signaling. Protein levels were determined by immunoblotting using specific antibodies. The results shown are representative of three independent experiments. Voa: voacangine-treated; Sun: sunitinib-treated.