Nintedanib is an Orally Active Triple Angiokinase Inhibitor for VEGFR, FGFR and PDGFR
Posted On 2021-11-07
VEGFR are receptors for vascular endothelial growth factor (VEGF). There are three main subtypes: VEGFR1/Flt-1, VEGFR2/KDR/Flk-1, and VEGFR3. VEGFR1 and 2 are expressed on vascular endothelial cells, whereas VEGFR3 is expressed on lymphatic endothelial. VEGFR1 and VEGFR2 play major roles in physiological as well as pathological angiogenesis. VEGFR3 can regulate angiogenesis at early embryogenesis but mostly function as critical regulators of lymphangiogenesis.
FGFR (Fibroblast growth factor receptors) are the receptors that bind to members of the fibroblast growth factor family of proteins. In vertebrates, five distinct membrane FGFR have been identified, and all of them belong to the tyrosine kinase superfamily (FGFR1, FGFR2, FGFR3, FGFR4, FGFR6). Besides, they are responsible for determining certain cells to become mesoderm, for the production of blood vessels, for limb outgrowth, and for the growth and differentiation of numerous cell types.
PDGFR (Platelet-derived growth factor receptors) are cell surface tyrosine kinase receptors for members of the platelet-derived growth factor (PDGF) family. There are two forms of the PDGFR: PDGFRα and PDGFRβ. The PDGF ligands can bind and dimerize PDGFRα/β. PDGF-A, -B and -C bind PDGFRα, whereas PDGF-B and -D bind PDGFRβ. What’s more, PDGFR regulates cell proliferation, cellular differentiation, cell growth, development and many diseases including cancer.
Nintedanib is a potent and orally active triple angiokinase inhibitor of VEGFR, FGFR and PDGFR.
Nintedanib is a potent and orally active triple vascular kinase inhibitor of VEGFR1/2/3, FGFR1/2/3 and PDGFRα/β. In vitro, Nintedanib inhibits mitogen-activated protein kinase and Akt signaling pathways. Therefore, it can inhibit the growth factor-dependent proliferation of HUVECs, HSMECs, HUASMCs, and BRPs. In addition, Nintedanib is highly active at well-tolerated doses. Moreover, Nintedanib is effective for the research of idiopathic pulmonary fibrosis and on-small-cell lung cancer. Meanwhile, it also inhibits tumor growth in a Caki-1 renal cancer mouse xenograft model.
All in all, Nintedanib is a potent triple angiokinase inhibitor for VEGFR1/2/3, FGFR1/2/3 and PDGFRα/β.
 Xie Y, et, al. Signal Transduct Target Ther. 2020 Sep 2;5(1):181.
 Papadopoulos N, et, al. Mol Aspects Med. 2018 Aug;62:75-88.