Tumor growth and development involve many complex pathways, such as malignant cell proliferation and angiogenesis. Kinases are the enzymes that control signal transduction in these pathways, including VEGF, PDGFR, c-kit, and so on. They are present in stromal vascular or cell-matrix, and when they are dysfunctional (such as overactivation), they may lead to tumors. Multikinase inhibitors can simultaneously act on multiple over-activated kinases and have been used to inhibit tumor growth. Moreover, these inhibitors can reduce the possibility of developing drug resistance. Henatinib, a derivative of Sunitinib, is an oral small-molecule multikinase inhibitor with broad and potent antiangiogenic and antitumor activities. Following the enzyme assay, Henatinib has highly inhibitory activity against VEGFR-2, c-kit, and PDGFR with IC₅₀s of 0.6 nM, 3.3 nM, and 41.5 nM, respectively.

Henatinib can inhibit cancer cells and tumor growth in vitro and in vivo.

In human umbilical vein endothelial cells (HUVEC), Henatinib markedly inhibits VEGFR-2 phosphorylation and its downstream signaling pathways and continuously represses VEGF-stimulated proliferation, migration, and tubule formation. In the human tumor xenograft model, this agent causes regression or growth arrest of tumors. Besides, bile secretion does not influence the absorption of Henatinib in rats, and its absorption and passive transportation are consistent. Neither agent concentration nor intestinal segments affect the absorption of Henatinib. In conclusion, Henatinib is a highly potent multikinase inhibitor targeting VEGF, PDGFR, and c-kit, with antiangiogenic and antitumor activities, and is well absorbed in the intestine.