Dihydroindazolocarbazoles(DHI-carbazoles) are the potent dual inhibitors to VEGFR2 and Tie-2. In this work

the mechanism of interaction between VEGFR2/Tie-2 and DHI-carbazoles was performed with Surflex-dock. The results from molecular docking indicated that DHI-carbazoles competitively bound to the active site

which was the substrate ATP in VEGFR2/Tie-2 with high affinity. The differences of activity between VEGFR2 and Tie-2 resulted from the minor difference of active pockets. Hydrophobic effect played a key role in the formation and stability. Hydrogen bond and electrostatic effect also contributed to the difference. This work elucidated the antitumor mechanism of the DHI-carbazoles as a dual potent inhibitor and provided theoretical basis for the design of tyrosine kinase inhibitors.